16-89917679-CAT-C

Variant names:

• chr16-89917679-CAT-C
• rs3212351
• ENST00000555427.1:c.-580-196_-580-195delAT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000570217.1(ENSG00000267048):​n.202-196_202-195delAT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (11664 hom., cov: 0)
• Consequence: ENSG00000267048 ENST00000570217.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 0.414

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]

LOC124903759 (HGNC:):

ACMG classification

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

• BP6: Variant 16-89917679-CAT-C is Benign according to our data. Variant chr16-89917679-CAT-C is described in ClinVar as [Benign]. Clinvar id is 1265010.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903759	XM_047435031.1	c.1041-196_1041-195delAT		intron_variant	Intron 2 of 3		XP_047290987.1
LOC124903759	XM_047435032.1	c.1041-147_1041-146delAT		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.-580-196_-580-195delAT		intron_variant	Intron 1 of 3	5		ENSP00000451760.1
MC1R	ENST00000639847.1	c.-580-196_-580-195delAT		intron_variant	Intron 1 of 2	5		ENSP00000492011.1
ENSG00000267048	ENST00000570217.1	n.202-196_202-195delAT		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58246 AN: 151830 Hom.: 11647 Cov.: 0

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.384 AC: 58298 AN: 151948 Hom.: 11664 Cov.: 0 AF XY: 0.395 AC XY: 29293 AN XY: 74250

African (AFR) AF: 0.415 AC: 17204 AN: 41428

American (AMR) AF: 0.478 AC: 7311 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1108 AN: 3466

East Asian (EAS) AF: 0.646 AC: 3327 AN: 5148

South Asian (SAS) AF: 0.473 AC: 2285 AN: 4828

European-Finnish (FIN) AF: 0.435 AC: 4580 AN: 10534

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21258 AN: 67944

Other (OTH) AF: 0.381 AC: 807 AN: 2116

Alfa AF: 0.346 Hom.: 1142

Bravo AF: 0.392

Asia WGS AF: 0.518 AC: 1807 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Macular degeneration, age-related, neovascular type Other:1

-

School of Pharmacy, University of Eastern Finland

Significance: association

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Publications

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Other links and lift over

dbSNP: rs3212351; hg19: chr16-89984087;