rs112676064

Variant names:

• chr10-76036098-A-G
• rs112676064
• NM_001305581.2:c.222A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001305581.2(LRMDA):​c.222A>G​(p.Leu74Leu) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.76
• Publications: 1 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 -20 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 VariationId is 730707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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.222A>G	p.Leu74Leu	synonymous	Exon 3 of 7	NP_001292510.1	A0A087WWI0
	LRMDA	NM_032024.5		c.138A>G	p.Leu46Leu	synonymous	Exon 2 of 6	NP_114413.1	Q9H2I8
	LRMDA	NR_131178.2		n.576A>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.222A>G	p.Leu74Leu	synonymous	Exon 3 of 7	ENSP00000480240.1	A0A087WWI0
	LRMDA	ENST00000372499.5	TSL:1	c.138A>G	p.Leu46Leu	synonymous	Exon 2 of 6	ENSP00000361577.1	Q9H2I8
	LRMDA	ENST00000593699.5	TSL:1	n.576A>G		non_coding_transcript_exon	Exon 4 of 8

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

GnomAD2 exomes AF: 0.00115 AC: 288 AN: 251402 AF XY: 0.000788

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 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

African (AFR) AF: 0.0156 AC: 522 AN: 33478

American (AMR) AF: 0.000470 AC: 21 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000698 AC: 4 AN: 5734

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1112010

Other (OTH) AF: 0.00106 AC: 64 AN: 60394

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

African (AFR) AF: 0.0159 AC: 660 AN: 41500

American (AMR) AF: 0.00229 AC: 35 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68002

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00247 Hom.: 1

Bravo AF: 0.00492

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.6
DANN	Benign	0.75
PhyloP100		4.8
PromoterAI		0.050	Neutral
Mutation Taster		=99/1	polymorphism

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: rs112676064; hg19: chr10-77795856;