chr6-44252339-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007355.4. 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
	HSP90AB1	NM_007355.4	MANE Select	c.1731+72T>C		intron	N/A	NP_031381.2
	HSP90AB1	NM_001271969.2		c.1731+72T>C		intron	N/A	NP_001258898.1	P08238
	HSP90AB1	NM_001271970.2		c.1731+72T>C		intron	N/A	NP_001258899.1	P08238

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSP90AB1	ENST00000371646.10	TSL:1 MANE Select	c.1731+72T>C		intron	N/A	ENSP00000360709.5	P08238
	HSP90AB1	ENST00000353801.7	TSL:1	c.1731+72T>C		intron	N/A	ENSP00000325875.3	P08238
	HSP90AB1	ENST00000371554.2	TSL:5	c.1731+72T>C		intron	N/A	ENSP00000360609.1	P08238

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

African (AFR) AF: 0.754 AC: 22080 AN: 29268

American (AMR) AF: 0.694 AC: 28828 AN: 41520

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 16792 AN: 22554

East Asian (EAS) AF: 0.727 AC: 28099 AN: 38676

South Asian (SAS) AF: 0.719 AC: 54451 AN: 75782

European-Finnish (FIN) AF: 0.740 AC: 29214 AN: 39458

Middle Eastern (MID) AF: 0.794 AC: 4185 AN: 5270

European-Non Finnish (NFE) AF: 0.709 AC: 673172 AN: 949220

Other (OTH) AF: 0.720 AC: 38474 AN: 53472

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

African (AFR) AF: 0.757 AC: 31386 AN: 41462

American (AMR) AF: 0.698 AC: 10664 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2527 AN: 3470

East Asian (EAS) AF: 0.702 AC: 3631 AN: 5172

South Asian (SAS) AF: 0.730 AC: 3518 AN: 4816

European-Finnish (FIN) AF: 0.752 AC: 7955 AN: 10580

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48445 AN: 67974

Other (OTH) AF: 0.738 AC: 1558 AN: 2112

Alfa AF: 0.721 Hom.: 158955

Bravo AF: 0.725

Asia WGS AF: 0.724 AC: 2521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.33
DANN	Benign	0.67
PhyloP100		-0.38
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: rs504697; hg19: chr6-44220076;