NM_002386.4:c.*157C>A

Variant names:

• chr16-89920369-C-A
• rs3212370
• NM_002386.4:c.*157C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002386.4(MC1R):​c.*157C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 680,126 control chromosomes in the GnomAD database, including 677 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (510 hom., cov: 33)
  • Exomes 𝑓: 0.0050 (167 hom.)
• Consequence: MC1R NM_002386.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.135
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-89920369-C-A is Benign according to our data. Variant chr16-89920369-C-A is described in ClinVar as Benign. ClinVar VariationId is 321445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002386.4. 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.*157C>A		3_prime_UTR	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.*157C>A		3_prime_UTR	Exon 1 of 1	ENSP00000451605.1	Q01726
	ENSG00000198211	ENST00000556922.1	TSL:2	c.950+161C>A		intron	N/A	ENSP00000451560.1	A0A0B4J269
	MC1R	ENST00000639847.1	TSL:5	c.*157C>A		3_prime_UTR	Exon 3 of 3	ENSP00000492011.1	Q01726

Frequencies

GnomAD3 genomes AF: 0.0432 AC: 6571 AN: 152120 Hom.: 508 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.00499 AC: 2636 AN: 527888 Hom.: 167 Cov.: 6 AF XY: 0.00427 AC XY: 1177 AN XY: 275342

African (AFR) AF: 0.147 AC: 1990 AN: 13540

American (AMR) AF: 0.0108 AC: 223 AN: 20558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14390

East Asian (EAS) AF: 0.00 AC: 0 AN: 31614

South Asian (SAS) AF: 0.000341 AC: 16 AN: 46864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44394

Middle Eastern (MID) AF: 0.00458 AC: 13 AN: 2838

European-Non Finnish (NFE) AF: 0.000181 AC: 59 AN: 325366

Other (OTH) AF: 0.0118 AC: 335 AN: 28324

GnomAD4 genome AF: 0.0432 AC: 6575 AN: 152238 Hom.: 510 Cov.: 33 AF XY: 0.0414 AC XY: 3084 AN XY: 74420

African (AFR) AF: 0.151 AC: 6260 AN: 41504

American (AMR) AF: 0.0152 AC: 232 AN: 15296

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

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

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68022

Other (OTH) AF: 0.0241 AC: 51 AN: 2116

Alfa AF: 0.0135 Hom.: 25

Bravo AF: 0.0493

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.83
DANN	Benign	0.61
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3212370; hg19: chr16-89986777;