chr16-89917760-C-A

Variant names:

• chr16-89917760-C-A
• rs192378666
• ENST00000555427.1:c.-580-116C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000570217.1(ENSG00000267048):​n.202-116C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00377 in 181,014 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (15 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: ENSG00000267048 ENST00000570217.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33
• Publications: 0 publications found

Genes affected

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]

ENSG00000267048 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-89917760-C-A is Benign according to our data. Variant chr16-89917760-C-A is described in ClinVar as [Benign]. Clinvar id is 1287143.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903759	XM_047435031.1	c.1041-116C>A		intron_variant	Intron 2 of 3		XP_047290987.1
LOC124903759	XM_047435032.1	c.1041-67C>A		intron_variant	Intron 2 of 2		XP_047290988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MC1R	ENST00000555427.1	c.-580-116C>A		intron_variant	Intron 1 of 3	5		ENSP00000451760.1
MC1R	ENST00000639847.1	c.-580-116C>A		intron_variant	Intron 1 of 2	5		ENSP00000492011.1
ENSG00000267048	ENST00000570217.1	n.202-116C>A		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.00445 AC: 677 AN: 152148 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000243 AC: 7 AN: 28748 Hom.: 0 AF XY: 0.000151 AC XY: 2 AN XY: 13208

African (AFR) AF: 0.00 AC: 0 AN: 950

American (AMR) AF: 0.00 AC: 0 AN: 622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1836

East Asian (EAS) AF: 0.000337 AC: 2 AN: 5938

South Asian (SAS) AF: 0.00 AC: 0 AN: 236

European-Finnish (FIN) AF: 0.0417 AC: 1 AN: 24

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 182

European-Non Finnish (NFE) AF: 0.000241 AC: 4 AN: 16626

Other (OTH) AF: 0.00 AC: 0 AN: 2334

GnomAD4 genome AF: 0.00444 AC: 676 AN: 152266 Hom.: 15 Cov.: 33 AF XY: 0.00660 AC XY: 491 AN XY: 74438

African (AFR) AF: 0.0000722 AC: 3 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0540 AC: 572 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00140 AC: 95 AN: 68020

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00397 Hom.: 0

Bravo AF: 0.000329

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 21, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.25
DANN	Benign	0.57
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs192378666; hg19: chr16-89984168;