rs2070635

Variant names:

• chr3-186618387-A-G
• rs2070635
• NM_001622.4:c.574-149A>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.574-149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,309,236 control chromosomes in the GnomAD database, including 136,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.36 (11868 hom., cov: 33)
  • Exomes 𝑓: 0.46 (124728 hom.)
• Consequence: AHSG NM_001622.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -2.07
• Publications: 17 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=-0.86).
• 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.574-149A>G		intron_variant	Intron 4 of 6	ENST00000411641.7	NP_001613.2
AHSG	NM_001354571.2	c.577-149A>G		intron_variant	Intron 4 of 6		NP_001341500.1
AHSG	NM_001354572.2	c.571-149A>G		intron_variant	Intron 4 of 6		NP_001341501.1
AHSG	NM_001354573.2	c.574-149A>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.574-149A>G		intron_variant	Intron 4 of 6	1	NM_001622.4	ENSP00000393887.2

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54365 AN: 152034 Hom.: 11865 Cov.: 33

Gnomad AFR AF: 0.0942

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.402

GnomAD4 exome AF: 0.458 AC: 529459 AN: 1157084 Hom.: 124728 AF XY: 0.461 AC XY: 260661 AN XY: 565496

African (AFR) AF: 0.0769 AC: 2041 AN: 26526

American (AMR) AF: 0.387 AC: 10251 AN: 26482

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 9066 AN: 18042

East Asian (EAS) AF: 0.594 AC: 19544 AN: 32906

South Asian (SAS) AF: 0.524 AC: 31482 AN: 60088

European-Finnish (FIN) AF: 0.386 AC: 14356 AN: 37238

Middle Eastern (MID) AF: 0.526 AC: 2263 AN: 4304

European-Non Finnish (NFE) AF: 0.463 AC: 418313 AN: 903224

Other (OTH) AF: 0.459 AC: 22143 AN: 48274

GnomAD4 genome AF: 0.357 AC: 54378 AN: 152152 Hom.: 11868 Cov.: 33 AF XY: 0.361 AC XY: 26858 AN XY: 74380

African (AFR) AF: 0.0941 AC: 3909 AN: 41544

American (AMR) AF: 0.387 AC: 5921 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1696 AN: 3472

East Asian (EAS) AF: 0.615 AC: 3175 AN: 5160

South Asian (SAS) AF: 0.543 AC: 2610 AN: 4808

European-Finnish (FIN) AF: 0.378 AC: 3997 AN: 10584

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.465 AC: 31623 AN: 67982

Other (OTH) AF: 0.402 AC: 851 AN: 2116

Alfa AF: 0.414 Hom.: 6990

Bravo AF: 0.347

Asia WGS AF: 0.510 AC: 1771 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Nephrolithiasis, calcium oxalate 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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0060
DANN	Benign	0.48
PhyloP100		-2.1
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: rs2070635; hg19: chr3-186336176; COSMIC: COSV56609751; COSMIC: COSV56609751;