10-76036098-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001305581.2(LRMDA):c.222A>G(p.Leu74=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000828 in 1,614,002 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (7 hom., cov: 31)
  • Exomes 𝑓: 0.00043 (6 hom.)
• Consequence: LRMDA NM_001305581.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.76

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 10-76036098-A-G is Benign according to our data. Variant chr10-76036098-A-G is described in ClinVar as [Benign]. Clinvar id is 730707.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-76036098-A-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00463 (705/152158) while in subpopulation AFR AF= 0.0159 (660/41500). AF 95% confidence interval is 0.0149. There are 7 homozygotes in gnomad4. There are 325 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRMDA	NM_001305581.2	c.222A>G	p.Leu74=	synonymous_variant	3/7	ENST00000611255.5
LRMDA	NM_032024.5	c.138A>G	p.Leu46=	synonymous_variant	2/6
LRMDA	NR_131178.2	n.576A>G		non_coding_transcript_exon_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRMDA	ENST00000611255.5	c.222A>G	p.Leu74=	synonymous_variant	3/7	5	NM_001305581.2	P1
LRMDA	ENST00000372499.5	c.138A>G	p.Leu46=	synonymous_variant	2/6	1
LRMDA	ENST00000593699.5	n.576A>G		non_coding_transcript_exon_variant	4/8	1
LRMDA	ENST00000593817.1	n.183A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.00458 AC: 697 AN: 152040 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00115 AC: 288 AN: 251402 Hom.: 1 AF XY: 0.000788 AC XY: 107 AN XY: 135864

Gnomad AFR exome AF: 0.0162

Gnomad AMR exome AF: 0.000405

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: 0.0000440

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000432 AC: 632 AN: 1461844 Hom.: 6 Cov.: 32 AF XY: 0.000380 AC XY: 276 AN XY: 727222

Gnomad4 AFR exome AF: 0.0156

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.00106

GnomAD4 genome AF: 0.00463 AC: 705 AN: 152158 Hom.: 7 Cov.: 31 AF XY: 0.00437 AC XY: 325 AN XY: 74408

Gnomad4 AFR AF: 0.0159

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00236 Hom.: 1

Bravo AF: 0.00492

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 09, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	6.6
Dann	Benign	0.75

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: rs112676064; hg19: chr10-77795856;