14-102081887-T-C

Position:

• chr14-102081887-T-C

Variant summary

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

The NM_005348.4(HSP90AA1):​c.2090-66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 846,106 control chromosomes in the GnomAD database, including 272,628 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 0.69 (40021 hom., cov: 31)
  • Exomes 𝑓: 0.81 (232607 hom.)
• Consequence: HSP90AA1 NM_005348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286

Genes affected

HSP90AA1 (HGNC:5253): (heat shock protein 90 alpha family class A member 1) The protein encoded by this gene is an inducible molecular chaperone that functions as a homodimer. The encoded protein aids in the proper folding of specific target proteins by use of an ATPase activity that is modulated by co-chaperones. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSP90AA1	NM_005348.4	c.2090-66A>G		intron_variant		ENST00000216281.13	NP_005339.3
HSP90AA1	NM_001017963.3	c.2456-66A>G		intron_variant			NP_001017963.2
HSP90AA1	XM_011536718.3	c.2453-66A>G		intron_variant			XP_011535020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSP90AA1	ENST00000216281.13	c.2090-66A>G		intron_variant		1	NM_005348.4	ENSP00000216281.8
HSP90AA1	ENST00000334701.11	c.2456-66A>G		intron_variant		1		ENSP00000335153.7

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105319 AN: 151928 Hom.: 40015 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.708

GnomAD4 exome AF: 0.814 AC: 564968 AN: 694060 Hom.: 232607 Cov.: 9 AF XY: 0.819 AC XY: 306256 AN XY: 373888

Gnomad4 AFR exome AF: 0.340

Gnomad4 AMR exome AF: 0.831

Gnomad4 ASJ exome AF: 0.827

Gnomad4 EAS exome AF: 0.777

Gnomad4 SAS exome AF: 0.845

Gnomad4 FIN exome AF: 0.794

Gnomad4 NFE exome AF: 0.836

Gnomad4 OTH exome AF: 0.795

GnomAD4 genome AF: 0.693 AC: 105347 AN: 152046 Hom.: 40021 Cov.: 31 AF XY: 0.697 AC XY: 51779 AN XY: 74308

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.837

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.710

Alfa AF: 0.807 Hom.: 41878

Bravo AF: 0.678

Asia WGS AF: 0.814 AC: 2832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.67

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: rs2298877; hg19: chr14-102548224; COSMIC: COSV53491670; COSMIC: COSV53491670;