rs6058017

Positions:

• chr20-34269192-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001672.3(ASIP):​c.*25A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,476,164 control chromosomes in the GnomAD database, including 26,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.28 (10483 hom., cov: 32)
  • Exomes 𝑓: 0.13 (16483 hom.)
• Consequence: ASIP NM_001672.3 3_prime_UTR
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.372

Genes affected

ASIP (HGNC:745): (agouti signaling protein) In mice, the agouti gene encodes a paracrine signaling molecule that causes hair follicle melanocytes to synthesize pheomelanin, a yellow pigment, instead of the black or brown pigment, eumelanin. Pleiotropic effects of constitutive expression of the mouse gene include adult-onset obesity, increased tumor susceptibility, and premature infertility. This gene is highly similar to the mouse gene and encodes a secreted protein that may (1) affect the quality of hair pigmentation, (2) act as a pharmacological antagonist of alpha-melanocyte-stimulating hormone, (3) play a role in neuroendocrine aspects of melanocortin action, and (4) have a functional role in regulating lipid metabolism in adipocytes. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIP	NM_001672.3	c.*25A>G		3_prime_UTR_variant	4/4	ENST00000374954.4	NP_001663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASIP	ENST00000374954.4	c.*25A>G		3_prime_UTR_variant	4/4	1	NM_001672.3	ENSP00000364092	P1
	ENST00000512005.1	n.147+11835T>C		intron_variant, non_coding_transcript_variant		3
ASIP	ENST00000568305.5			downstream_gene_variant		5		ENSP00000454804	P1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42442 AN: 152056 Hom.: 10463 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.239

GnomAD3 exomes AF: 0.151 AC: 13215 AN: 87524 Hom.: 1478 AF XY: 0.155 AC XY: 7397 AN XY: 47732

Gnomad AFR exome AF: 0.659

Gnomad AMR exome AF: 0.0848

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.216

Gnomad SAS exome AF: 0.212

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.129 AC: 170694 AN: 1323992 Hom.: 16483 Cov.: 32 AF XY: 0.130 AC XY: 84116 AN XY: 645926

Gnomad4 AFR exome AF: 0.697

Gnomad4 AMR exome AF: 0.0963

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.279 AC: 42493 AN: 152172 Hom.: 10483 Cov.: 32 AF XY: 0.276 AC XY: 20564 AN XY: 74416

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.238

Alfa AF: 0.190 Hom.: 1002

Bravo AF: 0.296

Asia WGS AF: 0.220 AC: 767 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

SKIN/HAIR/EYE PIGMENTATION 9, DARK/LIGHT HAIR Other:1

association, no assertion criteria provided

literature only

OMIM

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6058017; hg19: chr20-32856998;