chr6-44246680-A-C

Variant names:

• chr6-44246680-A-C
• rs3757283
• NM_001271970.2:c.-1+336A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001271970.2(HSP90AB1):​c.-1+336A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,108 control chromosomes in the GnomAD database, including 2,476 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 0.16 (2476 hom., cov: 32)
• Consequence: HSP90AB1 NM_001271970.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271970.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSP90AB1	NM_001271970.2		c.-1+336A>C		intron	N/A	NP_001258899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSP90AB1	ENST00000620073.4	TSL:5	c.-1+336A>C		intron	N/A	ENSP00000481908.1
	HSP90AB1	ENST00000874960.1		c.-1+445A>C		intron	N/A	ENSP00000545019.1
	HSP90AB1	ENST00000874961.1		c.-38+336A>C		intron	N/A	ENSP00000545020.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24278 AN: 151992 Hom.: 2475 Cov.: 32

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.160 AC: 24275 AN: 152108 Hom.: 2476 Cov.: 32 AF XY: 0.163 AC XY: 12101 AN XY: 74358

African (AFR) AF: 0.0377 AC: 1566 AN: 41530

American (AMR) AF: 0.221 AC: 3369 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3472

East Asian (EAS) AF: 0.363 AC: 1870 AN: 5154

South Asian (SAS) AF: 0.284 AC: 1371 AN: 4820

European-Finnish (FIN) AF: 0.192 AC: 2032 AN: 10580

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.191 AC: 12995 AN: 67972

Other (OTH) AF: 0.159 AC: 335 AN: 2106

Alfa AF: 0.184 Hom.: 7756

Bravo AF: 0.158

Asia WGS AF: 0.303 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.66
PhyloP100		-0.070
PromoterAI		0.00080	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3757283; hg19: chr6-44214417;