rs3212368

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is . The variant received -16 classification points (ACMG Germline Pathogenicity v2019): 0P and 16B. BA1BP4_StrongBP6_Strong

The NM_002386.4(MC1R):c.*12G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.00795 (AC=12,737) in the gnomAD database across 1,602,696 control chromosomes, including 944 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.15. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 499 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 445 hom. )

Consequence

MC1R
NM_002386.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.35

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

oculocutaneous albinism type 2
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

MC1R links:

ENSG00000198211 (HGNC:):

ENSG00000198211 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002386.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -16 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BP6

ClinVar 2-star benign — strong (BP6); ClinVar germline classification: Benign/Likely Benign, 2 star(s).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.1500 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_002386.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MC1R	NM_002386.4	MANE Select	c.*12G>A		3_prime_UTR	Exon 1 of 1	NP_002377.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MC1R	ENST00000555147.2	TSL:6 MANE Select	c.*12G>A	3_prime_UTR	Exon 1 of 1	ENSP00000451605.1	Q01726
ENSG00000198211	ENST00000556922.1	TSL:2	c.950+16G>A	intron	N/A	ENSP00000451560.1	A0A0B4J269
MC1R	ENST00000639847.1	TSL:5	c.*12G>A	3_prime_UTR	Exon 3 of 3	ENSP00000492011.1	Q01726

Frequencies

GnomAD3 genomes

AF:

0.0429

AC:

6536

AN:

152216

Hom.:

497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0253

GnomAD2 exomes

AF:

0.0110

AC:

2718

AN:

246400

AF XY:

0.00804

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.00791

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000261

Gnomad OTH exome

AF:

0.00449

GnomAD4 exome

AF:

0.00427

AC:

6196

AN:

1450362

Hom.:

445

Cov.:

AF XY:

0.00360

AC XY:

2601

AN XY:

721830

show subpopulations

African (AFR)

AF:

0.154

AC:

5093

AN:

33178

American (AMR)

AF:

0.00855

AC:

381

AN:

44548

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26046

East Asian (EAS)

AF:

0.00

AC:

AN:

39614

South Asian (SAS)

AF:

0.000395

AC:

AN:

85988

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00400

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.000104

AC:

115

AN:

1101936

Other (OTH)

AF:

0.00915

AC:

549

AN:

60008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

314

628

941

1255

1569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0429

AC:

6541

AN:

152334

Hom.:

499

Cov.:

AF XY:

0.0413

AC XY:

3073

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.150

AC:

6225

AN:

41564

American (AMR)

AF:

0.0150

AC:

229

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68030

Other (OTH)

AF:

0.0250

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

267

534

802

1069

1336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0302

Hom.:

147

Bravo

AF:

0.0491

Asia WGS

AF:

0.00577

AC:

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.00000800

AC:

AN:

122574

Turkish Variome

AF:

0.000609

AC:

AN:

6566

Hom.:

ABraOM SABE-WGS-1171

AF:

0.0290

AC:

AN:

2342

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Melanoma, cutaneous malignant, susceptibility to, 5 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.9

(source)

DANN

Benign

0.60

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over