14-102083502-A-G

Variant names:

• chr14-102083502-A-G
• rs7155973
• NM_005348.4:c.1486+44T>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.1486+44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 1,590,332 control chromosomes in the GnomAD database, including 694,067 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 0.92 (64808 hom., cov: 31)
  • Exomes 𝑓: 0.94 (629259 hom.)
• Consequence: HSP90AA1 NM_005348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 19 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005348.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSP90AA1	NM_005348.4	MANE Select	c.1486+44T>C		intron	N/A	NP_005339.3
	HSP90AA1	NM_001017963.3		c.1852+44T>C		intron	N/A	NP_001017963.2	P07900-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSP90AA1	ENST00000216281.13	TSL:1 MANE Select	c.1486+44T>C		intron	N/A	ENSP00000216281.8	P07900-1
	HSP90AA1	ENST00000334701.11	TSL:1	c.1852+44T>C		intron	N/A	ENSP00000335153.7	P07900-2
	HSP90AA1	ENST00000554401.1	TSL:1	n.*915+44T>C		intron	N/A	ENSP00000451400.1	H0YJF5

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140290 AN: 152140 Hom.: 64760 Cov.: 31

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.946

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.960

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.919

GnomAD2 exomes AF: 0.939 AC: 234364 AN: 249496 AF XY: 0.941

Gnomad AFR exome AF: 0.883

Gnomad AMR exome AF: 0.962

Gnomad ASJ exome AF: 0.936

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.915

Gnomad NFE exome AF: 0.928

Gnomad OTH exome AF: 0.938

GnomAD4 exome AF: 0.935 AC: 1344957 AN: 1438074 Hom.: 629259 Cov.: 26 AF XY: 0.936 AC XY: 671335 AN XY: 717144

African (AFR) AF: 0.881 AC: 29035 AN: 32964

American (AMR) AF: 0.959 AC: 42849 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 24339 AN: 25978

East Asian (EAS) AF: 1.00 AC: 39567 AN: 39572

South Asian (SAS) AF: 0.962 AC: 82503 AN: 85718

European-Finnish (FIN) AF: 0.913 AC: 47295 AN: 51818

Middle Eastern (MID) AF: 0.935 AC: 4879 AN: 5216

European-Non Finnish (NFE) AF: 0.932 AC: 1018631 AN: 1092570

Other (OTH) AF: 0.938 AC: 55859 AN: 59550

GnomAD4 genome AF: 0.922 AC: 140397 AN: 152258 Hom.: 64808 Cov.: 31 AF XY: 0.923 AC XY: 68728 AN XY: 74434

African (AFR) AF: 0.888 AC: 36915 AN: 41550

American (AMR) AF: 0.947 AC: 14476 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3264 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5186

South Asian (SAS) AF: 0.960 AC: 4636 AN: 4828

European-Finnish (FIN) AF: 0.909 AC: 9633 AN: 10600

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.929 AC: 63210 AN: 68024

Other (OTH) AF: 0.920 AC: 1939 AN: 2108

Alfa AF: 0.928 Hom.: 107397

Bravo AF: 0.923

Asia WGS AF: 0.973 AC: 3383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.88
DANN	Benign	0.37
PhyloP100		-0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7155973; hg19: chr14-102549839;