10-76339557-C-T

Variant names:

• chr10-76339557-C-T
• rs2395373
• NM_001305581.2:c.601+15072C>T

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+15072C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 151,950 control chromosomes in the GnomAD database, including 62,638 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 0.90 (62638 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.95 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	NM_001305581.2	MANE Select	c.601+15072C>T		intron	N/A	NP_001292510.1
	LRMDA	NM_032024.5		c.517+15072C>T		intron	N/A	NP_114413.1
	LRMDA	NR_131178.2		n.955+15072C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.601+15072C>T		intron	N/A	ENSP00000480240.1
	LRMDA	ENST00000372499.5	TSL:1	c.517+15072C>T		intron	N/A	ENSP00000361577.1
	LRMDA	ENST00000593699.5	TSL:1	n.955+15072C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137179 AN: 151832 Hom.: 62610 Cov.: 32

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.948

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.903

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

GnomAD4 genome AF: 0.903 AC: 137256 AN: 151950 Hom.: 62638 Cov.: 32 AF XY: 0.894 AC XY: 66437 AN XY: 74300

African (AFR) AF: 0.912 AC: 37863 AN: 41536

American (AMR) AF: 0.828 AC: 12642 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3181 AN: 3472

East Asian (EAS) AF: 0.555 AC: 2856 AN: 5142

South Asian (SAS) AF: 0.700 AC: 3368 AN: 4814

European-Finnish (FIN) AF: 0.890 AC: 9331 AN: 10490

Middle Eastern (MID) AF: 0.941 AC: 273 AN: 290

European-Non Finnish (NFE) AF: 0.956 AC: 64944 AN: 67922

Other (OTH) AF: 0.902 AC: 1896 AN: 2102

Alfa AF: 0.930 Hom.: 8026

Bravo AF: 0.897

Asia WGS AF: 0.618 AC: 2118 AN: 3424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.22
PhyloP100		-0.013
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: rs2395373; hg19: chr10-78099315;