rs151318945

Variant names:

• chr16-89920206-C-T
• rs151318945
• NM_002386.4:c.948C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The ENST00000556922.1(ENSG00000198211):​c.948C>T​(p.Ser316Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,612,908 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (6 hom.)
• Consequence: ENSG00000198211 ENST00000556922.1 splice_region, synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.141
• Publications: 8 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]

ENSG00000198211 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 16-89920206-C-T is Benign according to our data. Variant chr16-89920206-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 321442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.141 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000556922.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MC1R	NM_002386.4	MANE Select	c.948C>T	p.Ser316Ser	synonymous	Exon 1 of 1	NP_002377.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MC1R	ENST00000555147.2	TSL:6 MANE Select	c.948C>T	p.Ser316Ser	synonymous	Exon 1 of 1	ENSP00000451605.1	Q01726
	ENSG00000198211	ENST00000556922.1	TSL:2	c.948C>T	p.Ser316Ser	splice_region synonymous	Exon 1 of 5	ENSP00000451560.1	A0A0B4J269
	MC1R	ENST00000555427.1	TSL:5	c.948C>T	p.Ser316Ser	splice_region synonymous	Exon 3 of 4	ENSP00000451760.1	G3V4F0

Frequencies

GnomAD3 genomes AF: 0.00218 AC: 332 AN: 152248 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00385

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00170 AC: 422 AN: 248552 AF XY: 0.00174

Gnomad AFR exome AF: 0.000325

Gnomad AMR exome AF: 0.000667

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00307

Gnomad NFE exome AF: 0.00279

Gnomad OTH exome AF: 0.00215

GnomAD4 exome AF: 0.00233 AC: 3410 AN: 1460542 Hom.: 6 Cov.: 34 AF XY: 0.00236 AC XY: 1717 AN XY: 726542

African (AFR) AF: 0.000389 AC: 13 AN: 33432

American (AMR) AF: 0.000917 AC: 41 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86242

European-Finnish (FIN) AF: 0.00289 AC: 154 AN: 53360

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.00279 AC: 3095 AN: 1110876

Other (OTH) AF: 0.00169 AC: 102 AN: 60342

GnomAD4 genome AF: 0.00218 AC: 332 AN: 152366 Hom.: 1 Cov.: 33 AF XY: 0.00219 AC XY: 163 AN XY: 74512

African (AFR) AF: 0.000529 AC: 22 AN: 41586

American (AMR) AF: 0.000457 AC: 7 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00385 AC: 262 AN: 68040

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00244 Hom.: 0

Bravo AF: 0.00168

EpiCase AF: 0.00207

EpiControl AF: 0.00214

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	2	Melanoma, cutaneous malignant, susceptibility to, 5 (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.4
DANN	Benign	0.69
PhyloP100		0.14
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs151318945; hg19: chr16-89986614;