3-186619924-T-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.743T>C(p.Met248Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 1,611,398 control chromosomes in the GnomAD database, including 358,503 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 0.68 ( 35876 hom., cov: 31)

Exomes 𝑓: 0.66 ( 322627 hom. )

Consequence

AHSG
NM_001622.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.433

Publications

91 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=1.9404777E-6).

BP6

Variant 3-186619924-T-C is Benign according to our data. Variant chr3-186619924-T-C is described in ClinVar as Benign. ClinVar VariationId is 16043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
AHSG	NM_001622.4 link	c.743T>C	p.Met248Thr	missense_variant	Exon 6 of 7	ENST00000411641.7	NP_001613.2
AHSG	NM_001354571.2 link	c.746T>C	p.Met249Thr	missense_variant	Exon 6 of 7		NP_001341500.1
AHSG	NM_001354572.2 link	c.740T>C	p.Met247Thr	missense_variant	Exon 6 of 7		NP_001341501.1
AHSG	NM_001354573.2 link	c.676-662T>C		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.743T>C	p.Met248Thr	missense_variant	Exon 6 of 7	1	NM_001622.4	ENSP00000393887.2

Frequencies

GnomAD3 genomes

AF:

0.684

AC:

103930

AN:

151990

Hom.:

35853

Cov.:

show subpopulations

Gnomad AFR

AF:

0.746

Gnomad AMI

AF:

0.592

Gnomad AMR

AF:

0.626

Gnomad ASJ

AF:

0.761

Gnomad EAS

AF:

0.736

Gnomad SAS

AF:

0.797

Gnomad FIN

AF:

0.605

Gnomad MID

AF:

0.844

Gnomad NFE

AF:

0.655

Gnomad OTH

AF:

0.722

GnomAD2 exomes

AF:

0.676

AC:

168819

AN:

249888

AF XY:

0.685

show subpopulations

Gnomad AFR exome

AF:

0.750

Gnomad AMR exome

AF:

0.566

Gnomad ASJ exome

AF:

0.765

Gnomad EAS exome

AF:

0.735

Gnomad FIN exome

AF:

0.603

Gnomad NFE exome

AF:

0.662

Gnomad OTH exome

AF:

0.688

GnomAD4 exome

AF:

0.663

AC:

966968

AN:

1459290

Hom.:

322627

Cov.:

AF XY:

0.668

AC XY:

484685

AN XY:

726042

show subpopulations

African (AFR)

AF:

0.748

AC:

24960

AN:

33350

American (AMR)

AF:

0.573

AC:

25315

AN:

44216

Ashkenazi Jewish (ASJ)

AF:

0.765

AC:

19957

AN:

26094

East Asian (EAS)

AF:

0.738

AC:

29262

AN:

39670

South Asian (SAS)

AF:

0.789

AC:

67801

AN:

85972

European-Finnish (FIN)

AF:

0.605

AC:

32296

AN:

53348

Middle Eastern (MID)

AF:

0.839

AC:

4830

AN:

5760

European-Non Finnish (NFE)

AF:

0.649

AC:

721140

AN:

1110590

Other (OTH)

AF:

0.687

AC:

41407

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

14520

29041

43561

58082

72602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18978

37956

56934

75912

94890

<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:

0.684

AC:

104002

AN:

152108

Hom.:

35876

Cov.:

AF XY:

0.684

AC XY:

50859

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.745

AC:

30912

AN:

41476

American (AMR)

AF:

0.626

AC:

9570

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.761

AC:

2642

AN:

3470

East Asian (EAS)

AF:

0.736

AC:

3811

AN:

5180

South Asian (SAS)

AF:

0.797

AC:

3838

AN:

4818

European-Finnish (FIN)

AF:

0.605

AC:

6405

AN:

10586

Middle Eastern (MID)

AF:

0.849

AC:

248

AN:

292

European-Non Finnish (NFE)

AF:

0.655

AC:

44513

AN:

67984

Other (OTH)

AF:

0.723

AC:

1524

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1658

3316

4975

6633

8291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

824

1648

2472

3296

4120

<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:

0.674

Hom.:

152247

Bravo

AF:

0.686

TwinsUK

AF:

0.636

AC:

2358

ALSPAC

AF:

0.635

AC:

2446

ESP6500AA

AF:

0.750

AC:

3303

ESP6500EA

AF:

0.652

AC:

5607

ExAC

AF:

0.683

AC:

82916

Asia WGS

AF:

0.728

AC:

2533

AN:

3478

EpiCase

AF:

0.683

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

0.045

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.9

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0075

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.10

T;T

MetaRNN

Benign

0.0000019

T;T

MetaSVM

Benign

-1.0

PhyloP100

-0.43

PrimateAI

Benign

0.39

PROVEAN

Benign

2.4

N;N

REVEL

Benign

0.015

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.038

MPC

0.094

ClinPred

0.0025

GERP RS

-0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.033

gMVP

0.20

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