chr14-102086438-T-G

Variant names:

• chr14-102086438-T-G
• rs3736807
• NM_005348.4:c.1-60A>C

Variant summary

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

The NM_005348.4(HSP90AA1):​c.1-60A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 1,579,192 control chromosomes in the GnomAD database, including 532,282 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 (40103 hom., cov: 33)
  • Exomes 𝑓: 0.83 (492179 hom.)
• Consequence: HSP90AA1 NM_005348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738
• Publications: 17 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSP90AA1	NM_005348.4	c.1-60A>C		intron_variant	Intron 1 of 10	ENST00000216281.13	NP_005339.3
HSP90AA1	NM_001017963.3	c.367-60A>C		intron_variant	Intron 2 of 11		NP_001017963.2
HSP90AA1	XM_011536718.3	c.364-60A>C		intron_variant	Intron 2 of 11		XP_011535020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSP90AA1	ENST00000216281.13	c.1-60A>C		intron_variant	Intron 1 of 10	1	NM_005348.4	ENSP00000216281.8

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105461 AN: 152000 Hom.: 40097 Cov.: 33

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.709

GnomAD4 exome AF: 0.827 AC: 1179619 AN: 1427072 Hom.: 492179 AF XY: 0.829 AC XY: 590452 AN XY: 712468

African (AFR) AF: 0.326 AC: 10555 AN: 32330

American (AMR) AF: 0.831 AC: 37123 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 21455 AN: 25896

East Asian (EAS) AF: 0.779 AC: 30792 AN: 39512

South Asian (SAS) AF: 0.846 AC: 72372 AN: 85570

European-Finnish (FIN) AF: 0.796 AC: 42380 AN: 53274

Middle Eastern (MID) AF: 0.798 AC: 4549 AN: 5698

European-Non Finnish (NFE) AF: 0.844 AC: 912567 AN: 1080816

Other (OTH) AF: 0.807 AC: 47826 AN: 59300

GnomAD4 genome AF: 0.693 AC: 105489 AN: 152120 Hom.: 40103 Cov.: 33 AF XY: 0.697 AC XY: 51854 AN XY: 74352

African (AFR) AF: 0.347 AC: 14408 AN: 41506

American (AMR) AF: 0.804 AC: 12297 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2907 AN: 3472

East Asian (EAS) AF: 0.791 AC: 4089 AN: 5168

South Asian (SAS) AF: 0.839 AC: 4051 AN: 4828

European-Finnish (FIN) AF: 0.779 AC: 8240 AN: 10584

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 56928 AN: 67950

Other (OTH) AF: 0.711 AC: 1505 AN: 2116

Alfa AF: 0.768 Hom.: 91062

Bravo AF: 0.679

Asia WGS AF: 0.813 AC: 2828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.46
DANN	Benign	0.40
PhyloP100		-0.74
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3736807; hg19: chr14-102552775; COSMIC: COSV53491963; COSMIC: COSV53491963;