Genetic Variant AHSG:c.759+98T>C (chr3-186620038-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001622.4(AHSG):c.759+98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 829,960 control chromosomes in the GnomAD database, including 101,903 homozygotes. 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: 𝑓 0.46 ( 16760 hom., cov: 32)

Exomes 𝑓: 0.50 ( 85143 hom. )

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AHSG	NM_001622.4 link	c.759+98T>C	intron_variant	Intron 6 of 6	ENST00000411641.7	NP_001613.2	P02765
AHSG	NM_001354571.2 link	c.762+98T>C	intron_variant	Intron 6 of 6		NP_001341500.1
AHSG	NM_001354572.2 link	c.756+98T>C	intron_variant	Intron 6 of 6		NP_001341501.1
AHSG	NM_001354573.2 link	c.676-548T>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.759+98T>C		intron_variant	Intron 6 of 6	1	NM_001622.4	ENSP00000393887.2		P02765

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

70035

AN:

151950

Hom.:

16740

Cov.:

show subpopulations

Gnomad AFR

AF:

0.324

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.520

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.574

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.490

GnomAD4 exome

AF:

0.497

AC:

336646

AN:

677892

Hom.:

85143

AF XY:

0.501

AC XY:

173927

AN XY:

347388

show subpopulations

African (AFR)

AF:

0.313

AC:

5270

AN:

16860

American (AMR)

AF:

0.426

AC:

8408

AN:

19738

Ashkenazi Jewish (ASJ)

AF:

0.517

AC:

7595

AN:

14694

East Asian (EAS)

AF:

0.582

AC:

19193

AN:

33004

South Asian (SAS)

AF:

0.541

AC:

22245

AN:

41148

European-Finnish (FIN)

AF:

0.503

AC:

20755

AN:

41250

Middle Eastern (MID)

AF:

0.587

AC:

2337

AN:

3982

European-Non Finnish (NFE)

AF:

0.494

AC:

234409

AN:

474468

Other (OTH)

AF:

0.502

AC:

16434

AN:

32748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

8090

16180

24270

32360

40450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4672

9344

14016

18688

23360

<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:

0.461

AC:

70090

AN:

152068

Hom.:

16760

Cov.:

AF XY:

0.464

AC XY:

34503

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.324

AC:

13443

AN:

41512

American (AMR)

AF:

0.443

AC:

6773

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.520

AC:

1804

AN:

3472

East Asian (EAS)

AF:

0.612

AC:

3151

AN:

5148

South Asian (SAS)

AF:

0.575

AC:

2771

AN:

4820

European-Finnish (FIN)

AF:

0.504

AC:

5326

AN:

10564

Middle Eastern (MID)

AF:

0.602

AC:

177

AN:

294

European-Non Finnish (NFE)

AF:

0.517

AC:

35137

AN:

67966

Other (OTH)

AF:

0.491

AC:

1037

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1898

3796

5694

7592

9490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<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:

0.500

Hom.:

24745

Bravo

AF:

0.450

Asia WGS

AF:

0.542

AC:

1883

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.7

(source)

DANN

Benign

0.45

PhyloP100

0.35

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

Computational scores

Splicing

Publications

Other links and lift over