3-186618238-T-G

Variant summary

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

The NM_001622.4(AHSG):c.574-298T>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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
AHSG	NM_001622.4	c.574-298T>G		intron_variant		ENST00000411641.7
AHSG	NM_001354571.2	c.577-298T>G		intron_variant
AHSG	NM_001354572.2	c.571-298T>G		intron_variant
AHSG	NM_001354573.2	c.574-298T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHSG	ENST00000411641.7	c.574-298T>G		intron_variant		1	NM_001622.4	P3
HRG-AS1	ENST00000630178.2	n.239-38272A>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.506

Alfa AF: 0.506 Hom.: 2976

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

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	-0.90
Cadd	Benign	0.48
Dann	Benign	0.69

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: rs2070634; hg19: chr3-186336027;