chr16-89920200-A-G

Position:

chr16-89920200-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002386.4(MC1R):c.942A>G(p.Thr314=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,613,248 control chromosomes in the GnomAD database, including 19,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4915 hom., cov: 33)

Exomes 𝑓: 0.13 ( 14659 hom. )

Consequence

MC1R
NM_002386.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.194

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 16-89920200-A-G is Benign according to our data. Variant chr16-89920200-A-G is described in ClinVar as [Benign]. Clinvar id is 258655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.194 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MC1R	NM_002386.4 linkuse as main transcript	c.942A>G	p.Thr314=	synonymous_variant	1/1	ENST00000555147.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MC1R	ENST00000555147.2 linkuse as main transcript	c.942A>G	p.Thr314=	synonymous_variant	1/1		NM_002386.4	P1
	ENST00000554623.1 linkuse as main transcript	n.612T>C		non_coding_transcript_exon_variant	2/2	3
MC1R	ENST00000555427.1 linkuse as main transcript	c.942A>G	p.Thr314=	synonymous_variant	3/4	5
MC1R	ENST00000639847.1 linkuse as main transcript	c.942A>G	p.Thr314=	synonymous_variant	3/3	5		P1

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31298

AN:

152080

Hom.:

4896

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0841

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.0806

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.164

GnomAD3 exomes

AF:

0.143

AC:

35535

AN:

248648

Hom.:

3789

AF XY:

0.140

AC XY:

18874

AN XY:

135022

show subpopulations

Gnomad AFR exome

AF:

0.451

Gnomad AMR exome

AF:

0.0825

Gnomad ASJ exome

AF:

0.0805

Gnomad EAS exome

AF:

0.277

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.0816

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.127

AC:

185131

AN:

1461050

Hom.:

14659

Cov.:

AF XY:

0.127

AC XY:

92463

AN XY:

726836

show subpopulations

Gnomad4 AFR exome

AF:

0.453

Gnomad4 AMR exome

AF:

0.0825

Gnomad4 ASJ exome

AF:

0.0792

Gnomad4 EAS exome

AF:

0.187

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.0815

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.152

GnomAD4 genome

AF:

0.206

AC:

31355

AN:

152198

Hom.:

4915

Cov.:

AF XY:

0.200

AC XY:

14879

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.437

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.0841

Gnomad4 EAS

AF:

0.270

Gnomad4 SAS

AF:

0.204

Gnomad4 FIN

AF:

0.0806

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.166

Alfa

AF:

0.130

Hom.:

2068

Bravo

AF:

0.215

Asia WGS

AF:

0.254

AC:

883

AN:

3476

EpiCase

AF:

0.107

EpiControl

AF:

0.103

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Melanoma, cutaneous malignant, susceptibility to, 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.2

DANN

Benign

0.48

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

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