rs504697

Variant names:

• chr6-44252339-T-A
• rs504697
• NM_007355.4:c.1731+72T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-44252339-T-A
• chr6-44252339-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007355.4(HSP90AB1):​c.1731+72T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000795 in 1,257,224 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: HSP90AB1 NM_007355.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSP90AB1	NM_007355.4	c.1731+72T>A		intron_variant	Intron 10 of 11	ENST00000371646.10	NP_031381.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSP90AB1	ENST00000371646.10	c.1731+72T>A		intron_variant	Intron 10 of 11	1	NM_007355.4	ENSP00000360709.5
HSP90AB1	ENST00000353801.7	c.1731+72T>A		intron_variant	Intron 10 of 11	1		ENSP00000325875.3
HSP90AB1	ENST00000371554.2	c.1731+72T>A		intron_variant	Intron 10 of 11	5		ENSP00000360609.1
HSP90AB1	ENST00000620073.4	c.1731+72T>A		intron_variant	Intron 10 of 11	5		ENSP00000481908.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.95e-7 AC: 1 AN: 1257224 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 631292

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29330

American (AMR) AF: 0.00 AC: 0 AN: 41540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22580

East Asian (EAS) AF: 0.00 AC: 0 AN: 38696

South Asian (SAS) AF: 0.00 AC: 0 AN: 75850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5270

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 950922

Other (OTH) AF: 0.00 AC: 0 AN: 53552

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.27
DANN	Benign	0.73
PhyloP100		-0.38

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: rs504697; hg19: chr6-44220076;