rs10509370

Variant names:

• chr10-76356028-T-C
• rs10509370
• NM_001305581.2:c.601+31543T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001305581.2(LRMDA):​c.601+31543T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,078 control chromosomes in the GnomAD database, including 5,913 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5913 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799
• 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), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 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.601+31543T>C		intron	N/A	NP_001292510.1	A0A087WWI0
	LRMDA	NM_032024.5		c.517+31543T>C		intron	N/A	NP_114413.1	Q9H2I8
	LRMDA	NR_131178.2		n.955+31543T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.601+31543T>C		intron	N/A	ENSP00000480240.1	A0A087WWI0
	LRMDA	ENST00000372499.5	TSL:1	c.517+31543T>C		intron	N/A	ENSP00000361577.1	Q9H2I8
	LRMDA	ENST00000593699.5	TSL:1	n.955+31543T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38535 AN: 151960 Hom.: 5914 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0493

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.253 AC: 38526 AN: 152078 Hom.: 5913 Cov.: 32 AF XY: 0.249 AC XY: 18480 AN XY: 74326

African (AFR) AF: 0.118 AC: 4919 AN: 41526

American (AMR) AF: 0.192 AC: 2930 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 882 AN: 3462

East Asian (EAS) AF: 0.0490 AC: 254 AN: 5182

South Asian (SAS) AF: 0.132 AC: 633 AN: 4810

European-Finnish (FIN) AF: 0.343 AC: 3623 AN: 10560

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24214 AN: 67952

Other (OTH) AF: 0.256 AC: 542 AN: 2114

Alfa AF: 0.310 Hom.: 2712

Bravo AF: 0.239

Asia WGS AF: 0.0730 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.73
PhyloP100		-0.80
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: rs10509370; hg19: chr10-78115786;