rs1865644

Positions:

• chr10-76286292-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001305581.2(LRMDA):​c.517-38109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,590 control chromosomes in the GnomAD database, including 20,186 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 0.51 (20186 hom., cov: 33)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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]

LOC124902462 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.517-38109A>G		intron_variant		ENST00000611255.5	NP_001292510.1
LOC124902462	XR_007062203.1	n.3752T>C		non_coding_transcript_exon_variant	3/3
LRMDA	NM_032024.5	c.433-38109A>G		intron_variant			NP_114413.1
LRMDA	NR_131178.2	n.871-38109A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.517-38109A>G		intron_variant		5	NM_001305581.2	ENSP00000480240	P1
LRMDA	ENST00000372499.5	c.433-38109A>G		intron_variant		1		ENSP00000361577
LRMDA	ENST00000593699.5	n.871-38109A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77691 AN: 151474 Hom.: 20162 Cov.: 33

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.513 AC: 77755 AN: 151590 Hom.: 20186 Cov.: 33 AF XY: 0.514 AC XY: 38044 AN XY: 74042

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.516

Alfa AF: 0.486 Hom.: 29948

Bravo AF: 0.523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs1865644; hg19: chr10-78046050;