rs819136

Positions:

• chr20-34260913-G-A

Variant summary

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

The NM_001672.3(ASIP):​c.160+379G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,132 control chromosomes in the GnomAD database, including 7,132 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (7132 hom., cov: 32)
• Consequence: ASIP NM_001672.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIP	NM_001672.3	c.160+379G>A		intron_variant		ENST00000374954.4	NP_001663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASIP	ENST00000374954.4	c.160+379G>A		intron_variant		1	NM_001672.3	ENSP00000364092	P1
	ENST00000512005.1	n.148-10775C>T		intron_variant, non_coding_transcript_variant		3
ASIP	ENST00000568305.5	c.160+379G>A		intron_variant		5		ENSP00000454804	P1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35786 AN: 152014 Hom.: 7123 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.205

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.235 AC: 35818 AN: 152132 Hom.: 7132 Cov.: 32 AF XY: 0.233 AC XY: 17369 AN XY: 74400

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.204

Alfa AF: 0.121 Hom.: 3237

Bravo AF: 0.249

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs819136; hg19: chr20-32848719;