rs819135

Positions:

• chr20-34259961-A-G
• chr20-34259961-A-T

Variant summary

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

The NM_001672.3(ASIP):​c.-10-404A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,592 control chromosomes in the GnomAD database, including 28,439 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 0.58 (28439 hom., cov: 29)
• Consequence: ASIP NM_001672.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.953

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 = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIP	NM_001672.3	c.-10-404A>G		intron_variant		ENST00000374954.4	NP_001663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASIP	ENST00000374954.4	c.-10-404A>G		intron_variant		1	NM_001672.3	ENSP00000364092	P1
	ENST00000512005.1	n.148-9823T>C		intron_variant, non_coding_transcript_variant		3
ASIP	ENST00000568305.5	c.-10-404A>G		intron_variant		5		ENSP00000454804	P1

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87668 AN: 151474 Hom.: 28375 Cov.: 29

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.579 AC: 87788 AN: 151592 Hom.: 28439 Cov.: 29 AF XY: 0.575 AC XY: 42571 AN XY: 74052

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.562

Alfa AF: 0.559 Hom.: 3625

Bravo AF: 0.603

Asia WGS AF: 0.525 AC: 1826 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.75
DANN	Benign	0.83

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: rs819135; hg19: chr20-32847767;