XM_047435031.1:c.1117A>G

Variant names:

• chr16-89917952-A-G
• rs886052491
• XM_047435031.1:c.1117A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The XM_047435031.1(LOC124903759):​c.1117A>G​(p.Arg373Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 73,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: LOC124903759 XM_047435031.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315
• Publications: 0 publications found

Genes affected

LOC124903759 (HGNC:):

MC1R (HGNC:6929): (melanocortin 1 receptor) This intronless gene encodes the receptor protein for melanocyte-stimulating hormone (MSH). The encoded protein, a seven pass transmembrane G protein coupled receptor, controls melanogenesis. Two types of melanin exist: red pheomelanin and black eumelanin. Gene mutations that lead to a loss in function are associated with increased pheomelanin production, which leads to lighter skin and hair color. Eumelanin is photoprotective but pheomelanin may contribute to UV-induced skin damage by generating free radicals upon UV radiation. Binding of MSH to its receptor activates the receptor and stimulates eumelanin synthesis. This receptor is a major determining factor in sun sensitivity and is a genetic risk factor for melanoma and non-melanoma skin cancer. Over 30 variant alleles have been identified which correlate with skin and hair color, providing evidence that this gene is an important component in determining normal human pigment variation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903759	XM_047435031.1	c.1117A>G	p.Arg373Gly	missense_variant	Exon 3 of 4		XP_047290987.1
LOC124903759	XM_047435032.1	c.*107A>G		3_prime_UTR_variant	Exon 3 of 3		XP_047290988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000267048	ENST00000570217.1	n.278A>G		non_coding_transcript_exon_variant	Exon 3 of 3	4
MC1R	ENST00000555427.1	c.-504A>G		5_prime_UTR_variant	Exon 2 of 4	5		ENSP00000451760.1
MC1R	ENST00000639847.1	c.-504A>G		5_prime_UTR_variant	Exon 2 of 3	5		ENSP00000492011.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000137 AC: 1 AN: 73002 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 33800

African (AFR) AF: 0.00 AC: 0 AN: 3304

American (AMR) AF: 0.00 AC: 0 AN: 2206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4628

East Asian (EAS) AF: 0.00 AC: 0 AN: 10618

South Asian (SAS) AF: 0.00 AC: 0 AN: 630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 66

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 444

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 45060

Other (OTH) AF: 0.000165 AC: 1 AN: 6046

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.60
PhyloP100		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs886052491; hg19: chr16-89984360;