6-44247132-T-C

Variant names:

• chr6-44247132-T-C
• rs35074133
• NM_007355.4:c.-64T>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.-64T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,012 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: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: HSP90AB1 NM_007355.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.90
• Publications: 6 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=-0.79).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSP90AB1	NM_007355.4	MANE Select	c.-64T>C		5_prime_UTR	Exon 1 of 12	NP_031381.2
	HSP90AB1	NM_001271969.2		c.-77T>C		5_prime_UTR	Exon 1 of 12	NP_001258898.1
	HSP90AB1	NM_001271972.2		c.-64T>C		5_prime_UTR	Exon 1 of 12	NP_001258901.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSP90AB1	ENST00000371646.10	TSL:1 MANE Select	c.-64T>C		5_prime_UTR	Exon 1 of 12	ENSP00000360709.5
	HSP90AB1	ENST00000353801.7	TSL:1	c.-77T>C		5_prime_UTR	Exon 1 of 12	ENSP00000325875.3
	HSP90AB1	ENST00000620073.4	TSL:5	c.-1+788T>C		intron	N/A	ENSP00000481908.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152012 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152012 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74226

African (AFR) AF: 0.0000483 AC: 2 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 9

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.033
DANN	Benign	0.50
PhyloP100		-3.9
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs35074133; hg19: chr6-44214869;