chr10-76183065-T-G

Variant names:

• chr10-76183065-T-G
• rs1865641
• NM_001305581.2:c.516+124282T>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.516+124282T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,188 control chromosomes in the GnomAD database, including 2,575 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 0.15 (2575 hom., cov: 32)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• Publications: 4 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 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.516+124282T>G		intron	N/A	NP_001292510.1
	LRMDA	NM_032024.5		c.432+124282T>G		intron	N/A	NP_114413.1
	LRMDA	NR_131178.2		n.870+124282T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRMDA	ENST00000611255.5	TSL:5 MANE Select	c.516+124282T>G		intron	N/A	ENSP00000480240.1
	LRMDA	ENST00000372499.5	TSL:1	c.432+124282T>G		intron	N/A	ENSP00000361577.1
	LRMDA	ENST00000593699.5	TSL:1	n.870+124282T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23534 AN: 152070 Hom.: 2564 Cov.: 32

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.155 AC: 23557 AN: 152188 Hom.: 2575 Cov.: 32 AF XY: 0.163 AC XY: 12112 AN XY: 74412

African (AFR) AF: 0.0429 AC: 1783 AN: 41542

American (AMR) AF: 0.239 AC: 3655 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3472

East Asian (EAS) AF: 0.524 AC: 2699 AN: 5154

South Asian (SAS) AF: 0.274 AC: 1319 AN: 4816

European-Finnish (FIN) AF: 0.154 AC: 1635 AN: 10598

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11369 AN: 68010

Other (OTH) AF: 0.194 AC: 411 AN: 2116

Alfa AF: 0.163 Hom.: 1139

Bravo AF: 0.156

Asia WGS AF: 0.362 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.9
DANN	Benign	0.83
PhyloP100		0.28
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: rs1865641; hg19: chr10-77942823;