rs75852090

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001305581.2(LRMDA):c.611G>A(p.Gly204Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00509 in 1,613,916 control chromosomes in the GnomAD database, including 366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G204G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.028 ( 195 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 171 hom. )

Consequence

LRMDA
NM_001305581.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.57

Publications

5 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:

ENSG00000269256 (HGNC:):

ENSG00000269256 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=0.0043112934).

BP6

Variant 10-76557218-G-A is Benign according to our data. Variant chr10-76557218-G-A is described in ClinVar as Benign. ClinVar VariationId is 261992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
LRMDA	NM_001305581.2 link	c.611G>A	p.Gly204Glu	missense_variant	Exon 7 of 7	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5 link	c.527G>A	p.Gly176Glu	missense_variant	Exon 6 of 6		NP_114413.1
LRMDA	NR_131178.2 link	n.965G>A		non_coding_transcript_exon_variant	Exon 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5 link	c.611G>A	p.Gly204Glu	missense_variant	Exon 7 of 7	5	NM_001305581.2	ENSP00000480240.1

Frequencies

GnomAD3 genomes

AF:

0.0281

AC:

4266

AN:

152064

Hom.:

195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0960

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0229

GnomAD2 exomes

AF:

0.00717

AC:

1804

AN:

251456

AF XY:

0.00510

show subpopulations

Gnomad AFR exome

AF:

0.0991

Gnomad AMR exome

AF:

0.00414

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.00270

AC:

3942

AN:

1461734

Hom.:

171

Cov.:

AF XY:

0.00223

AC XY:

1619

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.0958

AC:

3207

AN:

33466

American (AMR)

AF:

0.00470

AC:

210

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000209

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00503

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000117

AC:

130

AN:

1111890

Other (OTH)

AF:

0.00576

AC:

348

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

177

354

530

707

884

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.0281

AC:

4270

AN:

152182

Hom.:

195

Cov.:

AF XY:

0.0267

AC XY:

1987

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0958

AC:

3974

AN:

41488

American (AMR)

AF:

0.0147

AC:

224

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68024

Other (OTH)

AF:

0.0227

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

186

373

559

746

932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.00942

Hom.:

206

Bravo

AF:

0.0319

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0910

AC:

401

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00906

AC:

1100

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;T;.

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

D;D;D

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-0.76

PhyloP100

5.6

PROVEAN

Pathogenic

-4.9

.;D;.

REVEL

Uncertain

0.42

Sift

Uncertain

0.0020

.;D;.

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.54

MVP

0.90

MPC

0.64

ClinPred

0.029

GERP RS

6.0

Varity_R

0.77

gMVP

0.64

Mutation Taster

=91/9

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

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