chr10-76047269-T-C

Position:

• chr10-76047269-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001305581.2(LRMDA):​c.364T>C​(p.Leu122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,612,926 control chromosomes in the GnomAD database, including 157,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14093 hom., cov: 32)
  • Exomes 𝑓: 0.43 (143295 hom.)
• Consequence: LRMDA NM_001305581.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.865

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 10-76047269-T-C is Benign according to our data. Variant chr10-76047269-T-C is described in ClinVar as [Benign]. Clinvar id is 261990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-76047269-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.865 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.364T>C	p.Leu122=	synonymous_variant	4/7	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.280T>C	p.Leu94=	synonymous_variant	3/6		NP_114413.1
LRMDA	NR_131178.2	n.718T>C		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.364T>C	p.Leu122=	synonymous_variant	4/7	5	NM_001305581.2	ENSP00000480240	P1
LRMDA	ENST00000372499.5	c.280T>C	p.Leu94=	synonymous_variant	3/6	1		ENSP00000361577
LRMDA	ENST00000593699.5	n.718T>C		non_coding_transcript_exon_variant	5/8	1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63602 AN: 151906 Hom.: 14069 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.00847

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.420

GnomAD3 exomes AF: 0.380 AC: 95250 AN: 250470 Hom.: 20903 AF XY: 0.386 AC XY: 52316 AN XY: 135366

Gnomad AFR exome AF: 0.427

Gnomad AMR exome AF: 0.210

Gnomad ASJ exome AF: 0.531

Gnomad EAS exome AF: 0.00676

Gnomad SAS exome AF: 0.315

Gnomad FIN exome AF: 0.528

Gnomad NFE exome AF: 0.460

Gnomad OTH exome AF: 0.419

GnomAD4 exome AF: 0.432 AC: 631808 AN: 1460902 Hom.: 143295 Cov.: 43 AF XY: 0.431 AC XY: 312939 AN XY: 726756

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.533

Gnomad4 EAS exome AF: 0.00746

Gnomad4 SAS exome AF: 0.323

Gnomad4 FIN exome AF: 0.525

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.419

GnomAD4 genome AF: 0.419 AC: 63666 AN: 152024 Hom.: 14093 Cov.: 32 AF XY: 0.417 AC XY: 30995 AN XY: 74320

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.00849

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.417

Alfa AF: 0.441 Hom.: 28160

Bravo AF: 0.403

Asia WGS AF: 0.182 AC: 637 AN: 3478

EpiCase AF: 0.458

EpiControl AF: 0.461

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 17, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Oculocutaneous albinism type 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.6
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs1898071; hg19: chr10-77807027; COSMIC: COSV65272743;