3-186618387-A-G

Position:

• chr3-186618387-A-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
AHSG	NM_001622.4	c.574-149A>G		intron_variant		ENST00000411641.7	NP_001613.2
AHSG	NM_001354571.2	c.577-149A>G		intron_variant			NP_001341500.1
AHSG	NM_001354572.2	c.571-149A>G		intron_variant			NP_001341501.1
AHSG	NM_001354573.2	c.574-149A>G		intron_variant			NP_001341502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHSG	ENST00000411641.7	c.574-149A>G		intron_variant		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

Gnomad4 AFR exome AF: 0.0769

Gnomad4 AMR exome AF: 0.387

Gnomad4 ASJ exome AF: 0.502

Gnomad4 EAS exome AF: 0.594

Gnomad4 SAS exome AF: 0.524

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.463

Gnomad4 OTH exome AF: 0.459

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

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.402

Alfa AF: 0.417 Hom.: 6020

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

association, no assertion criteria provided

case-control

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

Mar 01, 2014

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Computational scores

Source: dbNSFP v4.3

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