Genetic Variant NM_018368.4:c.473+2555C>T (chr6-69746786-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018368.4(LMBRD1):c.473+2555C>T variant causes a intron change. The variant allele was found at a frequency of 0.0636 in 170,136 control chromosomes in the GnomAD database, including 501 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.063 ( 459 hom., cov: 30)

Exomes 𝑓: 0.064 ( 42 hom. )

Consequence

LMBRD1
NM_018368.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.08

Publications

1 publications found

Variant links:

Genes affected

LMBRD1 (HGNC:23038): (LMBR1 domain containing 1) This gene encodes a lysosomal membrane protein that may be involved in the transport and metabolism of cobalamin. This protein also interacts with the large form of the hepatitis delta antigen and may be required for the nucleocytoplasmic shuttling of the hepatitis delta virus. Mutations in this gene are associated with the vitamin B12 metabolism disorder termed, homocystinuria-megaloblastic anemia complementation type F.[provided by RefSeq, Oct 2009]

LMBRD1 links:

GAPDHP42 (HGNC:37799): (glyceraldehyde 3 phosphate dehydrogenase pseudogene 42)

GAPDHP42 links:

LOC124901337 (HGNC:):

LOC124901337 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMBRD1	NM_018368.4 link	c.473+2555C>T		intron_variant	Intron 5 of 15	ENST00000649934.3	NP_060838.3	Q9NUN5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000649934.3 link	c.473+2555C>T		intron_variant	Intron 5 of 15		NM_018368.4	ENSP00000497690.1		Q9NUN5-1

Frequencies

GnomAD3 genomes

AF:

0.0635

AC:

9653

AN:

151968

Hom.:

458

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0165

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0829

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0768

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0824

Gnomad OTH

AF:

0.0580

GnomAD4 exome

AF:

0.0643

AC:

1160

AN:

18050

Hom.:

Cov.:

AF XY:

0.0638

AC XY:

681

AN XY:

10670

show subpopulations

African (AFR)

AF:

0.0104

AC:

AN:

676

American (AMR)

AF:

0.0849

AC:

176

AN:

2074

Ashkenazi Jewish (ASJ)

AF:

0.0258

AC:

AN:

310

East Asian (EAS)

AF:

0.00

AC:

AN:

1560

South Asian (SAS)

AF:

0.0560

AC:

AN:

1392

European-Finnish (FIN)

AF:

0.0915

AC:

120

AN:

1312

Middle Eastern (MID)

AF:

0.0556

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0718

AC:

706

AN:

9828

Other (OTH)

AF:

0.0731

AC:

AN:

862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

137

182

228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0635

AC:

9655

AN:

152086

Hom.:

459

Cov.:

AF XY:

0.0665

AC XY:

4942

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0165

AC:

683

AN:

41508

American (AMR)

AF:

0.0829

AC:

1267

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

AN:

3468

East Asian (EAS)

AF:

0.00194

AC:

AN:

5158

South Asian (SAS)

AF:

0.0779

AC:

375

AN:

4816

European-Finnish (FIN)

AF:

0.141

AC:

1487

AN:

10564

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0825

AC:

5605

AN:

67974

Other (OTH)

AF:

0.0564

AC:

119

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

451

902

1352

1803

2254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0785

Hom.:

279

Bravo

AF:

0.0553

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.5

(source)

DANN

Benign

0.73

PhyloP100

5.1

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over