14-102088215-T-C

Variant names:

• chr14-102088215-T-C
• rs4906178
• ENST00000334701.11:c.367-1837A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000334701.11(HSP90AA1):​c.367-1837A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,092 control chromosomes in the GnomAD database, including 49,974 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 0.80 (49974 hom., cov: 31)
• Consequence: HSP90AA1 ENST00000334701.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000334701.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSP90AA1	NM_001017963.3		c.367-1837A>G		intron	N/A	NP_001017963.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSP90AA1	ENST00000334701.11	TSL:1	c.367-1837A>G		intron	N/A	ENSP00000335153.7
	HSP90AA1	ENST00000557234.1	TSL:3	n.156-1837A>G		intron	N/A	ENSP00000452241.1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121359 AN: 151974 Hom.: 49952 Cov.: 31

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.805

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.798 AC: 121429 AN: 152092 Hom.: 49974 Cov.: 31 AF XY: 0.801 AC XY: 59585 AN XY: 74348

African (AFR) AF: 0.574 AC: 23789 AN: 41432

American (AMR) AF: 0.863 AC: 13189 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3049 AN: 3470

East Asian (EAS) AF: 0.790 AC: 4078 AN: 5160

South Asian (SAS) AF: 0.861 AC: 4164 AN: 4834

European-Finnish (FIN) AF: 0.875 AC: 9260 AN: 10588

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.899 AC: 61107 AN: 68002

Other (OTH) AF: 0.806 AC: 1700 AN: 2110

Alfa AF: 0.768 Hom.: 3077

Bravo AF: 0.786

Asia WGS AF: 0.843 AC: 2933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.49
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4906178; hg19: chr14-102554552; COSMIC: COSV53490610; COSMIC: COSV53490610;