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]

AHCY (HGNC:343): (adenosylhomocysteinase) S-adenosylhomocysteine hydrolase belongs to the adenosylhomocysteinase family. It catalyzes the reversible hydrolysis of S-adenosylhomocysteine (AdoHcy) to adenosine (Ado) and L-homocysteine (Hcy). Thus, it regulates the intracellular S-adenosylhomocysteine (SAH) concentration thought to be important for transmethylation reactions. Deficiency in this protein is one of the different causes of hypermethioninemia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

ENSG00000250917 (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	ENSP00000364092.3
ENSG00000250917	ENST00000512005.1	n.147+11835T>C		intron_variant		3
ASIP	ENST00000568305.5	c.*25A>G		downstream_gene_variant		5		ENSP00000454804.1

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;