1-46220120-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001013615.3(LURAP1):c.620A>G(p.Gln207Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,614,194 control chromosomes in the GnomAD database, including 1,132 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 74 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1058 hom. )

Consequence

LURAP1
NM_001013615.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.463

Publications

8 publications found

Variant links:

Genes affected

LURAP1 (HGNC:32327): (leucine rich adaptor protein 1) Involved in positive regulation of I-kappaB kinase/NF-kappaB signaling and positive regulation of cytokine production. Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

LURAP1 links:

POMGNT1 (HGNC:19139): (protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-)) This gene encodes a type II transmembrane protein that resides in the Golgi apparatus. It participates in O-mannosyl glycosylation and is specific for alpha linked terminal mannose. Mutations in this gene may be associated with muscle-eye-brain disease and several congenital muscular dystrophies. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Feb 2014]

POMGNT1 Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy type 2O
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Orphanet
muscle-eye-brain disease
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3
Inheritance: AR Classification: DEFINITIVE, LIMITED Submitted by: G2P, Ambry Genetics
myopathy caused by variation in POMGNT1
Inheritance: AR Classification: STRONG Submitted by: ClinGen
retinitis pigmentosa 76
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy with cerebellar involvement
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

POMGNT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020411909).

BP6

Variant 1-46220120-A-G is Benign according to our data. Variant chr1-46220120-A-G is described in ClinVar as Benign. ClinVar VariationId is 403064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0586 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013615.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LURAP1	NM_001013615.3	MANE Select	c.620A>G	p.Gln207Arg	missense	Exon 2 of 2	NP_001013633.1
	POMGNT1	NM_001243766.2		c.-466T>C		5_prime_UTR	Exon 1 of 23	NP_001230695.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LURAP1	ENST00000371980.4	TSL:1 MANE Select	c.620A>G	p.Gln207Arg	missense	Exon 2 of 2	ENSP00000361048.3
POMGNT1	ENST00000693223.1		n.183T>C		non_coding_transcript_exon	Exon 1 of 20
POMGNT1	ENST00000371992.1	TSL:2	c.-466T>C		5_prime_UTR	Exon 1 of 23	ENSP00000361060.1

Frequencies

GnomAD3 genomes

AF:

0.0254

AC:

3873

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00765

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0236

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00806

Gnomad FIN

AF:

0.0237

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0408

Gnomad OTH

AF:

0.0354

GnomAD2 exomes

AF:

0.0260

AC:

6482

AN:

248938

AF XY:

0.0263

show subpopulations

Gnomad AFR exome

AF:

0.00775

Gnomad AMR exome

AF:

0.0187

Gnomad ASJ exome

AF:

0.00864

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0252

Gnomad NFE exome

AF:

0.0414

Gnomad OTH exome

AF:

0.0335

GnomAD4 exome

AF:

0.0355

AC:

51852

AN:

1461850

Hom.:

1058

Cov.:

AF XY:

0.0346

AC XY:

25138

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00666

AC:

223

AN:

33480

American (AMR)

AF:

0.0196

AC:

876

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

272

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00943

AC:

813

AN:

86258

European-Finnish (FIN)

AF:

0.0280

AC:

1497

AN:

53384

Middle Eastern (MID)

AF:

0.0640

AC:

369

AN:

5766

European-Non Finnish (NFE)

AF:

0.0413

AC:

45962

AN:

1112008

Other (OTH)

AF:

0.0304

AC:

1838

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

3125

6250

9376

12501

15626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1704

3408

5112

6816

8520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0254

AC:

3873

AN:

152344

Hom.:

Cov.:

AF XY:

0.0243

AC XY:

1807

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.00762

AC:

317

AN:

41586

American (AMR)

AF:

0.0236

AC:

361

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00865

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00827

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0237

AC:

252

AN:

10622

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0408

AC:

2777

AN:

68022

Other (OTH)

AF:

0.0350

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

206

411

617

822

1028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0368

Hom.:

112

Bravo

AF:

0.0250

TwinsUK

AF:

0.0386

AC:

143

ALSPAC

AF:

0.0428

AC:

165

ESP6500AA

AF:

0.0113

AC:

ESP6500EA

AF:

0.0436

AC:

375

ExAC

AF:

0.0265

AC:

3217

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0406

EpiControl

AF:

0.0415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 425/13006=3.2%

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.3

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0039

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

0.46

PrimateAI

Benign

0.34

PROVEAN

Benign

0.30

REVEL

Benign

0.16

Sift

Benign

0.088

Sift4G

Benign

0.69

Polyphen

0.0

Vest4

0.012

MPC

0.23

ClinPred

0.0092

GERP RS

-3.1

PromoterAI

0.021

Neutral

(source)

Varity_R

0.061

gMVP

0.042

Mutation Taster

=299/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over