Variant 10-76036104-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001305581.2(LRMDA):c.228A>G(p.Arg76=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,613,902 control chromosomes in the GnomAD database, including 523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 40 hom., cov: 31)

Exomes 𝑓: 0.011 ( 483 hom. )

Consequence

LRMDA
NM_001305581.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.414

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 10-76036104-A-G is Benign according to our data. Variant chr10-76036104-A-G is described in ClinVar as [Benign]. Clinvar id is 261987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.414 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0741 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.228A>G	p.Arg76=	synonymous_variant	3/7	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5 linkuse as main transcript	c.144A>G	p.Arg48=	synonymous_variant	2/6		NP_114413.1
LRMDA	NR_131178.2 linkuse as main transcript	n.582A>G		non_coding_transcript_exon_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LRMDA	ENST00000611255.5 linkuse as main transcript	c.228A>G	p.Arg76=	synonymous_variant	3/7	5	NM_001305581.2	ENSP00000480240	P1
LRMDA	ENST00000372499.5 linkuse as main transcript	c.144A>G	p.Arg48=	synonymous_variant	2/6	1		ENSP00000361577
LRMDA	ENST00000593699.5 linkuse as main transcript	n.582A>G		non_coding_transcript_exon_variant	4/8	1
LRMDA	ENST00000593817.1 linkuse as main transcript	n.189A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1963

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00266

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0440

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.0806

Gnomad SAS

AF:

0.0218

Gnomad FIN

AF:

0.0250

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00512

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.0224

AC:

5625

AN:

251318

Hom.:

176

AF XY:

0.0208

AC XY:

2822

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.00314

Gnomad AMR exome

AF:

0.0651

Gnomad ASJ exome

AF:

0.00536

Gnomad EAS exome

AF:

0.0712

Gnomad SAS exome

AF:

0.0229

Gnomad FIN exome

AF:

0.0248

Gnomad NFE exome

AF:

0.00537

Gnomad OTH exome

AF:

0.0183

GnomAD4 exome

AF:

0.0110

AC:

16117

AN:

1461750

Hom.:

483

Cov.:

AF XY:

0.0112

AC XY:

8134

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00215

Gnomad4 AMR exome

AF:

0.0624

Gnomad4 ASJ exome

AF:

0.00444

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.0224

Gnomad4 FIN exome

AF:

0.0233

Gnomad4 NFE exome

AF:

0.00437

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.0129

AC:

1965

AN:

152152

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1173

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.0443

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.0805

Gnomad4 SAS

AF:

0.0212

Gnomad4 FIN

AF:

0.0250

Gnomad4 NFE

AF:

0.00512

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00571

Hom.:

Bravo

AF:

0.0133

Asia WGS

AF:

0.0550

AC:

189

AN:

3478

EpiCase

AF:

0.00469

EpiControl

AF:

0.00587

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.8

DANN

Benign

0.61

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