rs819136

Variant names:

• chr20-34260913-G-A
• rs819136
• NM_001672.3:c.160+379G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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]

ENSG00000250917 (HGNC:):

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]

AHCY Gene-Disease associations (from GenCC):

• hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ASIP	NM_001672.3	c.160+379G>A		intron_variant	Intron 2 of 3	ENST00000374954.4	NP_001663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIP	ENST00000374954.4	c.160+379G>A		intron_variant	Intron 2 of 3	1	NM_001672.3	ENSP00000364092.3
ASIP	ENST00000568305.5	c.160+379G>A		intron_variant	Intron 2 of 3	5		ENSP00000454804.1
ENSG00000250917	ENST00000512005.1	n.148-10775C>T		intron_variant	Intron 1 of 2	3

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

African (AFR) AF: 0.543 AC: 22503 AN: 41454

American (AMR) AF: 0.131 AC: 2008 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1119 AN: 5170

South Asian (SAS) AF: 0.194 AC: 932 AN: 4812

European-Finnish (FIN) AF: 0.116 AC: 1235 AN: 10616

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6855 AN: 68006

Other (OTH) AF: 0.204 AC: 431 AN: 2108

Alfa AF: 0.139 Hom.: 10828

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
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs819136; hg19: chr20-32848719;