Variant 14-102083784-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005348.4(HSP90AA1):c.1338+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,608,908 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 5 hom. )

Consequence

HSP90AA1
NM_005348.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.834

Variant links:

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]

HSP90AA1 links:

HSP90AA1 (HGNC:):

HSP90AA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-102083784-T-C is Benign according to our data. Variant chr14-102083784-T-C is described in ClinVar as [Benign]. Clinvar id is 785469.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00563 (857/152238) while in subpopulation AFR AF= 0.0196 (815/41534). AF 95% confidence interval is 0.0185. There are 8 homozygotes in gnomad4. There are 418 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 857 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
HSP90AA1	NM_005348.4 linkuse as main transcript	c.1338+9A>G	intron_variant	ENST00000216281.13	NP_005339.3	P07900-1K9JA46
HSP90AA1	NM_001017963.3 linkuse as main transcript	c.1704+9A>G	intron_variant		NP_001017963.2	P07900-2Q86SX1
HSP90AA1	XM_011536718.3 linkuse as main transcript	c.1701+9A>G	intron_variant		XP_011535020.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
HSP90AA1	ENST00000216281.13 linkuse as main transcript	c.1338+9A>G	intron_variant	1	NM_005348.4	ENSP00000216281.8	P07900-1
HSP90AA1	ENST00000334701.11 linkuse as main transcript	c.1704+9A>G	intron_variant	1		ENSP00000335153.7	P07900-2
HSP90AA1	ENST00000554401.1 linkuse as main transcript	n.*767+9A>G	intron_variant	1		ENSP00000451400.1	H0YJF5
HSP90AA1	ENST00000557089.1 linkuse as main transcript	n.442+9A>G	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00563

AC:

857

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00133

AC:

330

AN:

248224

Hom.:

AF XY:

0.000995

AC XY:

134

AN XY:

134616

show subpopulations

Gnomad AFR exome

AF:

0.0192

Gnomad AMR exome

AF:

0.000730

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000828

GnomAD4 exome

AF:

0.000523

AC:

762

AN:

1456670

Hom.:

Cov.:

AF XY:

0.000460

AC XY:

333

AN XY:

724652

show subpopulations

Gnomad4 AFR exome

AF:

0.0191

Gnomad4 AMR exome

AF:

0.000969

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000587

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000722

Gnomad4 OTH exome

AF:

0.00110

GnomAD4 genome

AF:

0.00563

AC:

857

AN:

152238

Hom.:

Cov.:

AF XY:

0.00562

AC XY:

418

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0196

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00339

Hom.:

Bravo

AF:

0.00633

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.19

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over