Variant 3-186620593-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001622.4(AHSG):c.767G>C(p.Ser256Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,592,390 control chromosomes in the GnomAD database, including 349,526 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33428 hom., cov: 31)

Exomes 𝑓: 0.66 ( 316098 hom. )

Consequence

AHSG
NM_001622.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.591

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:):

HRG-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4840803E-6).

BP6

Variant 3-186620593-G-C is Benign according to our data. Variant chr3-186620593-G-C is described in ClinVar as [Benign]. Clinvar id is 16044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHSG	NM_001622.4 linkuse as main transcript	c.767G>C	p.Ser256Thr	missense_variant	7/7	ENST00000411641.7	NP_001613.2	P02765
AHSG	NM_001354571.2 linkuse as main transcript	c.770G>C	p.Ser257Thr	missense_variant	7/7		NP_001341500.1
AHSG	NM_001354572.2 linkuse as main transcript	c.764G>C	p.Ser255Thr	missense_variant	7/7		NP_001341501.1
AHSG	NM_001354573.2 linkuse as main transcript	c.683G>C	p.Ser228Thr	missense_variant	6/6		NP_001341502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHSG	ENST00000411641.7 linkuse as main transcript	c.767G>C	p.Ser256Thr	missense_variant	7/7	1	NM_001622.4	ENSP00000393887.2		P02765

Frequencies

GnomAD3 genomes

AF:

0.661

AC:

100416

AN:

151850

Hom.:

33408

Cov.:

show subpopulations

Gnomad AFR

AF:

0.668

Gnomad AMI

AF:

0.592

Gnomad AMR

AF:

0.616

Gnomad ASJ

AF:

0.761

Gnomad EAS

AF:

0.735

Gnomad SAS

AF:

0.796

Gnomad FIN

AF:

0.605

Gnomad MID

AF:

0.839

Gnomad NFE

AF:

0.654

Gnomad OTH

AF:

0.704

GnomAD3 exomes

AF:

0.670

AC:

165931

AN:

247658

Hom.:

56374

AF XY:

0.681

AC XY:

91155

AN XY:

133870

show subpopulations

Gnomad AFR exome

AF:

0.671

Gnomad AMR exome

AF:

0.563

Gnomad ASJ exome

AF:

0.766

Gnomad EAS exome

AF:

0.736

Gnomad SAS exome

AF:

0.794

Gnomad FIN exome

AF:

0.604

Gnomad NFE exome

AF:

0.662

Gnomad OTH exome

AF:

0.684

GnomAD4 exome

AF:

0.660

AC:

951063

AN:

1440422

Hom.:

316098

Cov.:

AF XY:

0.665

AC XY:

473939

AN XY:

712262

show subpopulations

Gnomad4 AFR exome

AF:

0.671

Gnomad4 AMR exome

AF:

0.568

Gnomad4 ASJ exome

AF:

0.765

Gnomad4 EAS exome

AF:

0.738

Gnomad4 SAS exome

AF:

0.788

Gnomad4 FIN exome

AF:

0.605

Gnomad4 NFE exome

AF:

0.649

Gnomad4 OTH exome

AF:

0.682

GnomAD4 genome

AF:

0.661

AC:

100482

AN:

151968

Hom.:

33428

Cov.:

AF XY:

0.662

AC XY:

49145

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.668

Gnomad4 AMR

AF:

0.616

Gnomad4 ASJ

AF:

0.761

Gnomad4 EAS

AF:

0.735

Gnomad4 SAS

AF:

0.796

Gnomad4 FIN

AF:

0.605

Gnomad4 NFE

AF:

0.654

Gnomad4 OTH

AF:

0.705

Alfa

AF:

0.669

Hom.:

25743

Bravo

AF:

0.661

TwinsUK

AF:

0.636

AC:

2360

ALSPAC

AF:

0.635

AC:

2447

ESP6500AA

AF:

0.669

AC:

2946

ESP6500EA

AF:

0.652

AC:

5604

ExAC

AF:

0.675

AC:

81991

Asia WGS

AF:

0.723

AC:

2513

AN:

3478

EpiCase

AF:

0.682

EpiControl

AF:

0.687

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Alopecia-intellectual disability syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

RECLASSIFIED - AHSG POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jun 01, 2005

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.22

DANN

Benign

0.48

DEOGEN2

Benign

0.0020

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.068

T;T

MetaRNN

Benign

0.0000015

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

0.63

N;N

REVEL

Benign

0.0050

Sift

Benign

0.93

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0

.;B

Vest4

0.033

MPC

0.075

ClinPred

0.00013

GERP RS

-3.1

Varity_R

0.034

gMVP

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over