Variant 16-89917760-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000555427.1(MC1R):c.-580-116C>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

MC1R
ENST00000555427.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.33

Variant links:

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]

MC1R links:

LOC124903759 (HGNC:):

LOC124903759 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 AC in GnomAd4 at 676 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124903759	XM_047435031.1 link	c.1041-116C>A		intron_variant			XP_047290987.1
LOC124903759	XM_047435032.1 link	c.1041-67C>A		intron_variant			XP_047290988.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
MC1R	ENST00000555427.1 link	c.-580-116C>A	intron_variant	5	ENSP00000451760.1	G3V4F0
MC1R	ENST00000639847.1 link	c.-580-116C>A	intron_variant	5	ENSP00000492011.1	Q01726
ENSG00000267048	ENST00000570217.1 link	n.202-116C>A	intron_variant	4

Frequencies

GnomAD3 genomes

AF:

0.00445

AC:

677

AN:

152148

Hom.:

Cov.:

show subpopulations

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:

AN:

28748

Hom.:

AF XY:

0.000151

AC XY:

AN XY:

13208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000337

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0417

Gnomad4 NFE exome

AF:

0.000241

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00444

AC:

676

AN:

152266

Hom.:

Cov.:

AF XY:

0.00660

AC XY:

491

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0540

Gnomad4 NFE

AF:

0.00140

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00397

Hom.:

Bravo

AF:

0.000329

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.25

DANN

Benign

0.57

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over