Variant rs75852090 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein
LRMDA	NM_001305581.2 linkuse as main transcript	c.611G>A	p.Gly204Glu	missense_variant	7/7	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5 linkuse as main transcript	c.527G>A	p.Gly176Glu	missense_variant	6/6		NP_114413.1
LRMDA	NR_131178.2 linkuse as main transcript	n.965G>A		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5 linkuse as main transcript	c.611G>A	p.Gly204Glu	missense_variant	7/7	5	NM_001305581.2	ENSP00000480240	P1

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

GnomAD3 exomes

AF:

0.00717

AC:

1804

AN:

251456

Hom.:

AF XY:

0.00510

AC XY:

693

AN XY:

135898

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 SAS exome

AF:

0.0000980

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

Gnomad4 AFR exome

AF:

0.0958

Gnomad4 AMR exome

AF:

0.00470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.00576

GnomAD4 genome

AF:

0.0281

AC:

4270

AN:

152182

Hom.:

195

Cov.:

AF XY:

0.0267

AC XY:

1987

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0958

Gnomad4 AMR

AF:

0.0147

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.00509

Hom.:

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

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

MutationTaster

Benign

1.0

D;D

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over