Genetic Variant AHSA1:c.792+60T>C (chr14-77468244-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_012111.3(AHSA1):c.792+60T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,250,920 control chromosomes in the GnomAD database, including 11,278 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 0.11 ( 1107 hom., cov: 29)

Exomes 𝑓: 0.13 ( 10171 hom. )

Consequence

AHSA1
NM_012111.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.156

Publications

7 publications found

Variant links:

Genes affected

AHSA1 (HGNC:1189): (activator of HSP90 ATPase activity 1) Enables ATPase activator activity; Hsp90 protein binding activity; and chaperone binding activity. Involved in positive regulation of ATPase activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

AHSA1 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 (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHSA1	NM_012111.3 link	c.792+60T>C		intron_variant	Intron 7 of 8	ENST00000216479.8	NP_036243.1	O95433-1
AHSA1	NM_001321441.2 link	c.387+60T>C		intron_variant	Intron 7 of 8		NP_001308370.1	O95433G3V438

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHSA1	ENST00000216479.8 link	c.792+60T>C		intron_variant	Intron 7 of 8	1	NM_012111.3	ENSP00000216479.3		O95433-1

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16673

AN:

150882

Hom.:

1107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0666

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0195

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.146

GnomAD2 exomes

AF:

0.126

AC:

15767

AN:

125222

AF XY:

0.133

show subpopulations

Gnomad AFR exome

AF:

0.0653

Gnomad AMR exome

AF:

0.0932

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.0177

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.146

GnomAD4 exome

AF:

0.130

AC:

142495

AN:

1099922

Hom.:

10171

Cov.:

AF XY:

0.132

AC XY:

73176

AN XY:

553312

show subpopulations

African (AFR)

AF:

0.0655

AC:

1586

AN:

24202

American (AMR)

AF:

0.0887

AC:

2263

AN:

25524

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

2869

AN:

21770

East Asian (EAS)

AF:

0.0134

AC:

461

AN:

34282

South Asian (SAS)

AF:

0.211

AC:

14336

AN:

68072

European-Finnish (FIN)

AF:

0.128

AC:

6267

AN:

48822

Middle Eastern (MID)

AF:

0.250

AC:

1250

AN:

4992

European-Non Finnish (NFE)

AF:

0.130

AC:

107283

AN:

824654

Other (OTH)

AF:

0.130

AC:

6180

AN:

47604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

6242

12484

18727

24969

31211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3534

7068

10602

14136

17670

<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:

0.110

AC:

16671

AN:

150998

Hom.:

1107

Cov.:

AF XY:

0.111

AC XY:

8225

AN XY:

73770

show subpopulations

African (AFR)

AF:

0.0665

AC:

2758

AN:

41460

American (AMR)

AF:

0.116

AC:

1700

AN:

14698

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

421

AN:

3452

East Asian (EAS)

AF:

0.0193

AC:

100

AN:

5170

South Asian (SAS)

AF:

0.201

AC:

954

AN:

4744

European-Finnish (FIN)

AF:

0.124

AC:

1307

AN:

10540

Middle Eastern (MID)

AF:

0.302

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.133

AC:

9005

AN:

67646

Other (OTH)

AF:

0.145

AC:

304

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

733

1466

2200

2933

3666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<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:

0.132

Hom.:

2485

Bravo

AF:

0.105

Asia WGS

AF:

0.106

AC:

372

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.0

(source)

DANN

Benign

0.50

PhyloP100

-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

Computational scores

Splicing

Publications

Other links and lift over