rs3825694

Positions:

• chr14-77468244-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
AHSA1	NM_012111.3	c.792+60T>C		intron_variant		ENST00000216479.8	NP_036243.1
AHSA1	NM_001321441.2	c.387+60T>C		intron_variant			NP_001308370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHSA1	ENST00000216479.8	c.792+60T>C		intron_variant		1	NM_012111.3	ENSP00000216479.3

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16673 AN: 150882 Hom.: 1107 Cov.: 29

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

GnomAD3 exomes AF: 0.126 AC: 15767 AN: 125222 Hom.: 1123 AF XY: 0.133 AC XY: 8713 AN XY: 65674

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 SAS exome AF: 0.211

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.: 15 AF XY: 0.132 AC XY: 73176 AN XY: 553312

Gnomad4 AFR exome AF: 0.0655

Gnomad4 AMR exome AF: 0.0887

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.0134

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.128

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.110 AC: 16671 AN: 150998 Hom.: 1107 Cov.: 29 AF XY: 0.111 AC XY: 8225 AN XY: 73770

Gnomad4 AFR AF: 0.0665

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0193

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.145

Alfa AF: 0.136 Hom.: 2086

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
DANN	Benign	0.50

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

LitVar

Other links and lift over

dbSNP: rs3825694; hg19: chr14-77934587; COSMIC: COSV53633297; COSMIC: COSV53633297;