20-34197406-C-G

Position:

• chr20-34197406-C-G

Variant summary

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

The NM_001385218.1(ASIP):​c.-11+2646C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,156 control chromosomes in the GnomAD database, including 6,991 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 0.17 (6991 hom., cov: 31)
• Consequence: ASIP NM_001385218.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIP	NM_001385218.1	c.-11+2646C>G		intron_variant			NP_001372147.1
ASIP	XM_011528821.1	c.-79+10845C>G		intron_variant			XP_011527123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASIP	ENST00000568305.5	c.-11+2646C>G		intron_variant		5		ENSP00000454804	P1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25096 AN: 152038 Hom.: 6982 Cov.: 31

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0672

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00175

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.165 AC: 25139 AN: 152156 Hom.: 6991 Cov.: 31 AF XY: 0.159 AC XY: 11854 AN XY: 74420

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.0670

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00175

Gnomad4 OTH AF: 0.118

Alfa AF: 0.111 Hom.: 420

Bravo AF: 0.189

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.014
DANN	Benign	0.48

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: rs6119471; hg19: chr20-32785212;