rs3757286

chr6-44247637-T-A

Variant summary

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

The NM_007355.4(HSP90AB1):c.-1+442T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 152,278 control chromosomes in the GnomAD database, including 799 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 0.084 (799 hom., cov: 32)
• Consequence: HSP90AB1 NM_007355.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

Genes affected

HSP90AB1 (HGNC:5258): (heat shock protein 90 alpha family class B member 1) This gene encodes a member of the heat shock protein 90 family; these proteins are involved in signal transduction, protein folding and degradation and morphological evolution. This gene encodes the constitutive form of the cytosolic 90 kDa heat-shock protein and is thought to play a role in gastric apoptosis and inflammation. Alternative splicing results in multiple transcript variants. Pseudogenes have been identified on multiple chromosomes. [provided by RefSeq, Dec 2012]

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSP90AB1	NM_007355.4	c.-1+442T>A		intron_variant		ENST00000371646.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSP90AB1	ENST00000371646.10	c.-1+442T>A		intron_variant		1	NM_007355.4	P1
HSP90AB1	ENST00000353801.7	c.-14+442T>A		intron_variant		1		P1
HSP90AB1	ENST00000620073.4	c.1-993T>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0839 AC: 12768 AN: 152160 Hom.: 797 Cov.: 32

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0558

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0931

Gnomad OTH AF: 0.0795

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

GnomAD4 genome AF: 0.0839 AC: 12782 AN: 152278 Hom.: 799 Cov.: 32 AF XY: 0.0865 AC XY: 6440 AN XY: 74452

Gnomad4 AFR AF: 0.0198

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.0558

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.0524

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0931

Gnomad4 OTH AF: 0.0810

Alfa AF: 0.0963 Hom.: 101

Bravo AF: 0.0814

Asia WGS AF: 0.175 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	1.8
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3757286; hg19: chr6-44215374;