Genetic Variant AHSG:c.759+98T>A (chr3-186620038-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001622.4(AHSG):c.759+98T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AHSG
NM_001622.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.346

Publications

19 publications found

Variant links:

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]

AHSG links:

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

HRG-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AHSG	NM_001622.4 link	c.759+98T>A	intron_variant	Intron 6 of 6	ENST00000411641.7	NP_001613.2	P02765
AHSG	NM_001354571.2 link	c.762+98T>A	intron_variant	Intron 6 of 6		NP_001341500.1
AHSG	NM_001354572.2 link	c.756+98T>A	intron_variant	Intron 6 of 6		NP_001341501.1
AHSG	NM_001354573.2 link	c.676-548T>A	intron_variant	Intron 5 of 5		NP_001341502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHSG	ENST00000411641.7 link	c.759+98T>A		intron_variant	Intron 6 of 6	1	NM_001622.4	ENSP00000393887.2		P02765

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

680604

Hom.:

AF XY:

0.00

AC XY:

AN XY:

348808

African (AFR)

AF:

0.00

AC:

AN:

16904

American (AMR)

AF:

0.00

AC:

AN:

19790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14730

East Asian (EAS)

AF:

0.00

AC:

AN:

33076

South Asian (SAS)

AF:

0.00

AC:

AN:

41370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3992

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

476482

Other (OTH)

AF:

0.00

AC:

AN:

32878

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.1

(source)

DANN

Benign

0.48

PhyloP100

0.35

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over