dbSNP rs2070635: AHSG:c.574-149A>G (chr3-186618387-A-G) – 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.574-149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,309,236 control chromosomes in the GnomAD database, including 136,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.36 ( 11868 hom., cov: 33)

Exomes 𝑓: 0.46 ( 124728 hom. )

Consequence

AHSG
NM_001622.4 intron

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: -2.07

Publications

17 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001622.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AHSG	NM_001622.4	MANE Select	c.574-149A>G	intron	N/A	NP_001613.2	P02765
AHSG	NM_001354571.2		c.577-149A>G	intron	N/A	NP_001341500.1	C9JV77
AHSG	NM_001354572.2		c.571-149A>G	intron	N/A	NP_001341501.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AHSG	ENST00000411641.7	TSL:1 MANE Select	c.574-149A>G	intron	N/A	ENSP00000393887.2	P02765
AHSG	ENST00000864095.1		c.574-110A>G	intron	N/A	ENSP00000534154.1
AHSG	ENST00000864081.1		c.574-125A>G	intron	N/A	ENSP00000534140.1

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54365

AN:

152034

Hom.:

11865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0942

Gnomad AMI

AF:

0.495

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.616

Gnomad SAS

AF:

0.542

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.465

Gnomad OTH

AF:

0.402

GnomAD4 exome

AF:

0.458

AC:

529459

AN:

1157084

Hom.:

124728

AF XY:

0.461

AC XY:

260661

AN XY:

565496

show subpopulations

African (AFR)

AF:

0.0769

AC:

2041

AN:

26526

American (AMR)

AF:

0.387

AC:

10251

AN:

26482

Ashkenazi Jewish (ASJ)

AF:

0.502

AC:

9066

AN:

18042

East Asian (EAS)

AF:

0.594

AC:

19544

AN:

32906

South Asian (SAS)

AF:

0.524

AC:

31482

AN:

60088

European-Finnish (FIN)

AF:

0.386

AC:

14356

AN:

37238

Middle Eastern (MID)

AF:

0.526

AC:

2263

AN:

4304

European-Non Finnish (NFE)

AF:

0.463

AC:

418313

AN:

903224

Other (OTH)

AF:

0.459

AC:

22143

AN:

48274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

12975

25950

38926

51901

64876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12850

25700

38550

51400

64250

<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:

0.357

AC:

54378

AN:

152152

Hom.:

11868

Cov.:

AF XY:

0.361

AC XY:

26858

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0941

AC:

3909

AN:

41544

American (AMR)

AF:

0.387

AC:

5921

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

1696

AN:

3472

East Asian (EAS)

AF:

0.615

AC:

3175

AN:

5160

South Asian (SAS)

AF:

0.543

AC:

2610

AN:

4808

European-Finnish (FIN)

AF:

0.378

AC:

3997

AN:

10584

Middle Eastern (MID)

AF:

0.500

AC:

146

AN:

292

European-Non Finnish (NFE)

AF:

0.465

AC:

31623

AN:

67982

Other (OTH)

AF:

0.402

AC:

851

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1639

3278

4916

6555

8194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.414

Hom.:

6990

Bravo

AF:

0.347

Asia WGS

AF:

0.510

AC:

1771

AN:

3478

ClinVar

ClinVar submissions

Significance:association

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nephrolithiasis, calcium oxalate (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0060

(source)

DANN

Benign

0.48

PhyloP100

-2.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over