rs7101263

Variant names:

• chr10-76285505-T-G
• rs7101263
• NM_001305581.2:c.517-38896T>G

Variant summary

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

The NM_001305581.2(LRMDA):​c.517-38896T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 152,266 control chromosomes in the GnomAD database, including 196 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 0.030 (196 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet

LOC124902462 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.517-38896T>G		intron_variant	Intron 5 of 6	ENST00000611255.5	NP_001292510.1
LOC124902462	XR_007062203.1	n.4539A>C		non_coding_transcript_exon_variant	Exon 3 of 3
LRMDA	NM_032024.5	c.433-38896T>G		intron_variant	Intron 4 of 5		NP_114413.1
LRMDA	NR_131178.2	n.871-38896T>G		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-38896T>G		intron_variant	Intron 5 of 6	5	NM_001305581.2	ENSP00000480240.1
LRMDA	ENST00000372499.5	c.433-38896T>G		intron_variant	Intron 4 of 5	1		ENSP00000361577.1
LRMDA	ENST00000593699.5	n.871-38896T>G		intron_variant	Intron 6 of 7	1

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4556 AN: 152148 Hom.: 194 Cov.: 32

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.0486

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00146

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0300 AC: 4570 AN: 152266 Hom.: 196 Cov.: 32 AF XY: 0.0290 AC XY: 2156 AN XY: 74458

African (AFR) AF: 0.0936 AC: 3888 AN: 41532

American (AMR) AF: 0.0129 AC: 197 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3470

East Asian (EAS) AF: 0.0486 AC: 252 AN: 5190

South Asian (SAS) AF: 0.00435 AC: 21 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00146 AC: 99 AN: 68010

Other (OTH) AF: 0.0279 AC: 59 AN: 2114

Alfa AF: 0.0335 Hom.: 20

Bravo AF: 0.0337

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.51
PhyloP100		-1.0
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: rs7101263; hg19: chr10-78045263;