rs2070634

Variant names:

• chr3-186618238-T-G
• rs2070634
• NM_001622.4:c.574-298T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001622.4(AHSG):​c.574-298T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,936 control chromosomes in the GnomAD database, including 17,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.48 (17767 hom., cov: 31)
• Consequence: AHSG NM_001622.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.792
• Publications: 5 publications found

Genes affected

AHSG (HGNC:349): (alpha 2-HS glycoprotein) The protein encoded by this gene is a negatively-charged serum glycoprotein that is synthesized by hepatocytes. The encoded protein consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. It is involved in several processes, including endocytosis, brain development, and the formation of bone tissue. Defects in this gene are a cause of susceptibility to leanness. [provided by RefSeq, Aug 2017]

HRG-AS1 (HGNC:55915): (HRG and FETUB antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHSG	NM_001622.4	c.574-298T>G		intron_variant	Intron 4 of 6	ENST00000411641.7	NP_001613.2
AHSG	NM_001354571.2	c.577-298T>G		intron_variant	Intron 4 of 6		NP_001341500.1
AHSG	NM_001354572.2	c.571-298T>G		intron_variant	Intron 4 of 6		NP_001341501.1
AHSG	NM_001354573.2	c.574-298T>G		intron_variant	Intron 4 of 5		NP_001341502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHSG	ENST00000411641.7	c.574-298T>G		intron_variant	Intron 4 of 6	1	NM_001622.4	ENSP00000393887.2

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72196 AN: 151818 Hom.: 17751 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.476 AC: 72247 AN: 151936 Hom.: 17767 Cov.: 31 AF XY: 0.479 AC XY: 35542 AN XY: 74266

African (AFR) AF: 0.345 AC: 14285 AN: 41428

American (AMR) AF: 0.451 AC: 6884 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1921 AN: 3472

East Asian (EAS) AF: 0.615 AC: 3163 AN: 5144

South Asian (SAS) AF: 0.605 AC: 2911 AN: 4812

European-Finnish (FIN) AF: 0.506 AC: 5348 AN: 10564

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 35985 AN: 67924

Other (OTH) AF: 0.506 AC: 1067 AN: 2110

Alfa AF: 0.501 Hom.: 3034

Bravo AF: 0.466

Asia WGS AF: 0.559 AC: 1942 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Calcium oxalate urolithiasis Other:1

Mar 01, 2014

Division of Molecular Genetics and Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.48
DANN	Benign	0.69
PhyloP100		-0.79
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: rs2070634; hg19: chr3-186336027;