chr10-76036104-A-G

Variant names:

• chr10-76036104-A-G
• rs60420182
• NM_001305581.2:c.228A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001305581.2(LRMDA):​c.228A>G​(p.Arg76Arg) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.414
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 7

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305581.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	NM_001305581.2	MANE Select	c.228A>G	p.Arg76Arg	synonymous	Exon 3 of 7	NP_001292510.1	A0A087WWI0
	LRMDA	NM_032024.5		c.144A>G	p.Arg48Arg	synonymous	Exon 2 of 6	NP_114413.1	Q9H2I8
	LRMDA	NR_131178.2		n.582A>G		non_coding_transcript_exon	Exon 4 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.228A>G	p.Arg76Arg	synonymous	Exon 3 of 7	ENSP00000480240.1	A0A087WWI0
	LRMDA	ENST00000372499.5	TSL:1	c.144A>G	p.Arg48Arg	synonymous	Exon 2 of 6	ENSP00000361577.1	Q9H2I8
	LRMDA	ENST00000593699.5	TSL:1	n.582A>G		non_coding_transcript_exon	Exon 4 of 8

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1963 AN: 152034 Hom.: 40 Cov.: 31

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

GnomAD2 exomes AF: 0.0224 AC: 5625 AN: 251318 AF XY: 0.0208

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 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.: 32 AF XY: 0.0112 AC XY: 8134 AN XY: 727178

African (AFR) AF: 0.00215 AC: 72 AN: 33480

American (AMR) AF: 0.0624 AC: 2788 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00444 AC: 116 AN: 26136

East Asian (EAS) AF: 0.110 AC: 4377 AN: 39686

South Asian (SAS) AF: 0.0224 AC: 1931 AN: 86246

European-Finnish (FIN) AF: 0.0233 AC: 1245 AN: 53418

Middle Eastern (MID) AF: 0.00980 AC: 56 AN: 5714

European-Non Finnish (NFE) AF: 0.00437 AC: 4854 AN: 1111986

Other (OTH) AF: 0.0112 AC: 678 AN: 60388

GnomAD4 genome AF: 0.0129 AC: 1965 AN: 152152 Hom.: 40 Cov.: 31 AF XY: 0.0158 AC XY: 1173 AN XY: 74400

African (AFR) AF: 0.00265 AC: 110 AN: 41522

American (AMR) AF: 0.0443 AC: 678 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.0805 AC: 414 AN: 5140

South Asian (SAS) AF: 0.0212 AC: 102 AN: 4814

European-Finnish (FIN) AF: 0.0250 AC: 265 AN: 10594

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00512 AC: 348 AN: 68000

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00604 Hom.: 6

Bravo AF: 0.0133

Asia WGS AF: 0.0550 AC: 189 AN: 3478

EpiCase AF: 0.00469

EpiControl AF: 0.00587

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.8
DANN	Benign	0.61
PhyloP100		0.41
PromoterAI		-0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs60420182; hg19: chr10-77795862; COSMIC: COSV65270714;