Variant 10-75782995-TC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001305581.2(LRMDA):c.132-253012del variant causes a intron 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
NM_001305581.2 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 6.86

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 -9 ACMG points.

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 id is 261988.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1, Likely_benign=1}.

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRMDA	NM_001305581.2 linkuse as main transcript	c.132-253012del		intron_variant		ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5 linkuse as main transcript	c.21del	p.Ser8AlafsTer14	frameshift_variant	1/6		NP_114413.1
LRMDA	NR_131178.2 linkuse as main transcript	n.86-99660del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LRMDA	ENST00000372499.5 linkuse as main transcript	c.21del	p.Ser8AlafsTer14	frameshift_variant	1/6	1		ENSP00000361577
LRMDA	ENST00000611255.5 linkuse as main transcript	c.132-253012del		intron_variant		5	NM_001305581.2	ENSP00000480240	P1
LRMDA	ENST00000593699.5 linkuse as main transcript	n.86-99660del		intron_variant, non_coding_transcript_variant		1
LRMDA	ENST00000593817.1 linkuse as main transcript	n.92+181665del		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes

AF:

0.00400

AC:

1003

AN:

251006

Hom.:

AF XY:

0.00346

AC XY:

469

AN XY:

135690

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 SAS exome

AF:

0.000261

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

Gnomad4 AFR exome

AF:

0.0302

Gnomad4 AMR exome

AF:

0.00436

Gnomad4 ASJ exome

AF:

0.0160

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00101

Gnomad4 OTH exome

AF:

0.00551

GnomAD4 genome

AF:

0.00974

AC:

1483

AN:

152258

Hom.:

Cov.:

AF XY:

0.00936

AC XY:

697

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0289

Gnomad4 AMR

AF:

0.00595

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.0119

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

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	LRMDA: BS1, BS2 -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 22, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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