Genetic Variant LRRC75A:p.Arg231His (chr17-16443931-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001113567.3(LRRC75A):c.692G>A(p.Arg231His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,613,034 control chromosomes in the GnomAD database, including 148 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 0.0044 ( 25 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 123 hom. )

Consequence

LRRC75A
NM_001113567.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.49

Publications

2 publications found

Variant links:

Genes affected

LRRC75A (HGNC:32403): (leucine rich repeat containing 75A) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LRRC75A links:

SNHG29 (HGNC:28619): (small nucleolar RNA host gene 29)

SNHG29 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=0.004951209).

BP6

Variant 17-16443931-C-T is Benign according to our data. Variant chr17-16443931-C-T is described in ClinVar as Benign. ClinVar VariationId is 788905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113567.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC75A	NM_001113567.3	MANE Select	c.692G>A	p.Arg231His	missense	Exon 4 of 4	NP_001107039.1	Q8NAA5-1
LRRC75A	NM_207387.4		c.576G>A	p.Pro192Pro	synonymous	Exon 3 of 3	NP_997270.2	Q8NAA5-2
SNHG29	NR_027171.1		n.554+2801C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC75A	ENST00000470794.2	TSL:1 MANE Select	c.692G>A	p.Arg231His	missense	Exon 4 of 4	ENSP00000419502.1	Q8NAA5-1
LRRC75A	ENST00000409887.3	TSL:1	n.803G>A		non_coding_transcript_exon	Exon 3 of 3
SNHG29	ENST00000581361.5	TSL:1	n.181+3678C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00440

AC:

669

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00810

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00622

GnomAD2 exomes

AF:

0.00915

AC:

2287

AN:

250078

AF XY:

0.00719

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.0586

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00936

Gnomad NFE exome

AF:

0.0000972

Gnomad OTH exome

AF:

0.00605

GnomAD4 exome

AF:

0.00231

AC:

3371

AN:

1460720

Hom.:

123

Cov.:

AF XY:

0.00205

AC XY:

1489

AN XY:

726674

show subpopulations

African (AFR)

AF:

0.000597

AC:

AN:

33480

American (AMR)

AF:

0.0595

AC:

2661

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.000394

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00897

AC:

473

AN:

52758

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000522

AC:

AN:

1111624

Other (OTH)

AF:

0.00205

AC:

124

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

219

437

656

874

1093

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.00444

AC:

676

AN:

152314

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

380

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.000818

AC:

AN:

41570

American (AMR)

AF:

0.0344

AC:

526

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00810

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68018

Other (OTH)

AF:

0.00616

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000980

Hom.:

Bravo

AF:

0.00671

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00685

AC:

832

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

Eigen

Benign

-0.035

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.36

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0050

MetaSVM

Benign

-1.1

PhyloP100

1.5

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.2

REVEL

Benign

0.041

Sift

Benign

0.18

Sift4G

Benign

0.37

Polyphen

0.064

Vest4

0.091

MVP

0.043

MPC

0.62

ClinPred

0.012

GERP RS

4.3

Varity_R

0.091

gMVP

0.25

Mutation Taster

=92/8

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

Computational scores

Splicing

Publications

Other links and lift over