3-186620593-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/20 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

Publications

87 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein
AHSG	NM_001622.4 link	c.767G>C	p.Ser256Thr	missense_variant	Exon 7 of 7	ENST00000411641.7	NP_001613.2
AHSG	NM_001354571.2 link	c.770G>C	p.Ser257Thr	missense_variant	Exon 7 of 7		NP_001341500.1
AHSG	NM_001354572.2 link	c.764G>C	p.Ser255Thr	missense_variant	Exon 7 of 7		NP_001341501.1
AHSG	NM_001354573.2 link	c.683G>C	p.Ser228Thr	missense_variant	Exon 6 of 6		NP_001341502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHSG	ENST00000411641.7 link	c.767G>C	p.Ser256Thr	missense_variant	Exon 7 of 7	1	NM_001622.4	ENSP00000393887.2

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

GnomAD2 exomes

AF:

0.670

AC:

165931

AN:

247658

AF XY:

0.681

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 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

African (AFR)

AF:

0.671

AC:

22209

AN:

33120

American (AMR)

AF:

0.568

AC:

24956

AN:

43966

Ashkenazi Jewish (ASJ)

AF:

0.765

AC:

19593

AN:

25624

East Asian (EAS)

AF:

0.738

AC:

28880

AN:

39152

South Asian (SAS)

AF:

0.788

AC:

67479

AN:

85586

European-Finnish (FIN)

AF:

0.605

AC:

32148

AN:

53108

Middle Eastern (MID)

AF:

0.837

AC:

4775

AN:

5708

European-Non Finnish (NFE)

AF:

0.649

AC:

710584

AN:

1094832

Other (OTH)

AF:

0.682

AC:

40439

AN:

59326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

16260

32520

48780

65040

81300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18950

37900

56850

75800

94750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.661

AC:

100482

AN:

151968

Hom.:

33428

Cov.:

AF XY:

0.662

AC XY:

49145

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.668

AC:

27679

AN:

41426

American (AMR)

AF:

0.616

AC:

9409

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.761

AC:

2641

AN:

3470

East Asian (EAS)

AF:

0.735

AC:

3783

AN:

5148

South Asian (SAS)

AF:

0.796

AC:

3838

AN:

4820

European-Finnish (FIN)

AF:

0.605

AC:

6384

AN:

10552

Middle Eastern (MID)

AF:

0.844

AC:

248

AN:

294

European-Non Finnish (NFE)

AF:

0.654

AC:

44477

AN:

67956

Other (OTH)

AF:

0.705

AC:

1487

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1732

3464

5196

6928

8660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

RECLASSIFIED - AHSG POLYMORPHISM

Benign:1

Jun 01, 2005

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

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

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.0

.;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

MutationAssessor

Benign

0.0

.;.

PhyloP100

-0.59

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

Vest4

0.033

ClinPred

0.00013

GERP RS

-3.1

Varity_R

0.034

gMVP

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over