chr6-44247637-T-A

Variant names:

• chr6-44247637-T-A
• rs3757286
• NM_007355.4:c.-1+442T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 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.-1+442T>A		intron	N/A	NP_031381.2
	HSP90AB1	NM_001271969.2		c.-14+442T>A		intron	N/A	NP_001258898.1	P08238
	HSP90AB1	NM_001271970.2		c.1-993T>A		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.-1+442T>A		intron	N/A	ENSP00000360709.5	P08238
	HSP90AB1	ENST00000353801.7	TSL:1	c.-14+442T>A		intron	N/A	ENSP00000325875.3	P08238
	HSP90AB1	ENST00000874964.1		c.-993T>A		5_prime_UTR	Exon 1 of 11	ENSP00000545023.1

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

African (AFR) AF: 0.0198 AC: 823 AN: 41580

American (AMR) AF: 0.123 AC: 1886 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0558 AC: 193 AN: 3458

East Asian (EAS) AF: 0.296 AC: 1530 AN: 5176

South Asian (SAS) AF: 0.0524 AC: 253 AN: 4830

European-Finnish (FIN) AF: 0.137 AC: 1455 AN: 10614

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0931 AC: 6330 AN: 68006

Other (OTH) AF: 0.0810 AC: 171 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.8
DANN	Benign	0.50
PhyloP100		-1.4
PromoterAI		-0.028	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3757286; hg19: chr6-44215374;