rs504697

chr6-44252339-T-C

Variant summary

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

The NM_007355.4(HSP90AB1):c.1731+72T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,407,296 control chromosomes in the GnomAD database, including 360,627 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 0.73 (40229 hom., cov: 32)
  • Exomes 𝑓: 0.71 (320398 hom.)
• Consequence: HSP90AB1 NM_007355.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSP90AB1	NM_007355.4	c.1731+72T>C		intron_variant		ENST00000371646.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSP90AB1	ENST00000371646.10	c.1731+72T>C		intron_variant		1	NM_007355.4	P1
HSP90AB1	ENST00000353801.7	c.1731+72T>C		intron_variant		1		P1
HSP90AB1	ENST00000371554.2	c.1731+72T>C		intron_variant		5		P1
HSP90AB1	ENST00000620073.4	c.1731+72T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110392 AN: 151958 Hom.: 40195 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.740

GnomAD4 exome AF: 0.713 AC: 895295 AN: 1255220 Hom.: 320398 AF XY: 0.714 AC XY: 450068 AN XY: 630328

Gnomad4 AFR exome AF: 0.754

Gnomad4 AMR exome AF: 0.694

Gnomad4 ASJ exome AF: 0.745

Gnomad4 EAS exome AF: 0.727

Gnomad4 SAS exome AF: 0.719

Gnomad4 FIN exome AF: 0.740

Gnomad4 NFE exome AF: 0.709

Gnomad4 OTH exome AF: 0.720

GnomAD4 genome AF: 0.726 AC: 110480 AN: 152076 Hom.: 40229 Cov.: 32 AF XY: 0.728 AC XY: 54124 AN XY: 74334

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.738

Alfa AF: 0.720 Hom.: 68253

Bravo AF: 0.725

Asia WGS AF: 0.724 AC: 2521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.33
Dann	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs504697; hg19: chr6-44220076;