rs146123023

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 4P and 9B. PVS1_StrongBP6BS1BS2

The ENST00000372499.5(LRMDA):c.21delC(p.Ser8AlafsTer14) variant causes a frameshift change. The variant allele was found at a frequency of 0.00287 in 1,614,100 control chromosomes in the GnomAD database, including 63 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0097 ( 20 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 43 hom. )

Consequence

LRMDA
ENST00000372499.5 frameshift

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 6.86

Publications

9 publications found

Variant links:

Genes affected

LRMDA (HGNC:23405): (leucine rich melanocyte differentiation associated) This gene encodes a leucine-rich repeat protein. The encoded protein is thought to play a role in melanocyte differentiation. Mutations in this gene have been associated with autosomal recessive oculocutaneous albinism 7 (OCA7). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

LRMDA Gene-Disease associations (from GenCC):

oculocutaneous albinism type 7
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

LRMDA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 8 pathogenic variants in the truncated region.

BP6

Variant 10-75782995-TC-T is Benign according to our data. Variant chr10-75782995-TC-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 261988.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00974 (1483/152258) while in subpopulation AFR AF = 0.0289 (1201/41562). AF 95% confidence interval is 0.0275. There are 20 homozygotes in GnomAd4. There are 697 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2 link	c.132-253012delC		intron_variant	Intron 2 of 6	ENST00000611255.5	NP_001292510.1	A0A087WWI0
LRMDA	NM_032024.5 link	c.21delC	p.Ser8AlafsTer14	frameshift_variant	Exon 1 of 6		NP_114413.1	Q9H2I8
LRMDA	NR_131178.2 link	n.86-99660delC		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRMDA	ENST00000372499.5 link	c.21delC	p.Ser8AlafsTer14	frameshift_variant	Exon 1 of 6	1		ENSP00000361577.1	Q9H2I8
LRMDA	ENST00000611255.5 link	c.132-253012delC		intron_variant	Intron 2 of 6	5	NM_001305581.2	ENSP00000480240.1	A0A087WWI0
LRMDA	ENST00000593699.5 link	n.86-99660delC		intron_variant	Intron 1 of 7	1
LRMDA	ENST00000593817.1 link	n.92+181665delC		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.00975

AC:

1483

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00596

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.00400

AC:

1003

AN:

251006

AF XY:

0.00346

show subpopulations

Gnomad AFR exome

AF:

0.0301

Gnomad AMR exome

AF:

0.00390

Gnomad ASJ exome

AF:

0.0177

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00141

Gnomad OTH exome

AF:

0.00555

GnomAD4 exome

AF:

0.00216

AC:

3152

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

1525

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.0302

AC:

1010

AN:

33478

American (AMR)

AF:

0.00436

AC:

195

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0160

AC:

417

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000174

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00936

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00101

AC:

1127

AN:

1112000

Other (OTH)

AF:

0.00551

AC:

333

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

175

350

524

699

874

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.00974

AC:

1483

AN:

152258

Hom.:

Cov.:

AF XY:

0.00936

AC XY:

697

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0289

AC:

1201

AN:

41562

American (AMR)

AF:

0.00595

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00125

AC:

AN:

68004

Other (OTH)

AF:

0.0119

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

147

221

294

368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000830

Hom.:

Bravo

AF:

0.0119

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00240

EpiControl

AF:

0.00219

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

LRMDA: BS1, BS2 -

Feb 22, 2017

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.9

Mutation Taster

=31/169

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over