rs35074133

Positions:

• chr6-44247132-T-A
• chr6-44247132-T-C
• chr6-44247132-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_007355.4(HSP90AB1):​c.-64T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0318 in 152,188 control chromosomes in the GnomAD database, including 119 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 0.032 (119 hom., cov: 32)
  • Exomes 𝑓: 0.044 (0 hom.)
• Consequence: HSP90AB1 NM_007355.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.90

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]

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0318 (4839/152120) while in subpopulation NFE AF= 0.049 (3333/67970). AF 95% confidence interval is 0.0476. There are 119 homozygotes in gnomad4. There are 2257 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4839 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSP90AB1	NM_007355.4	c.-64T>A		5_prime_UTR_variant	1/12	ENST00000371646.10	NP_031381.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSP90AB1	ENST00000371646.10	c.-64T>A		5_prime_UTR_variant	1/12	1	NM_007355.4	ENSP00000360709	P1
HSP90AB1	ENST00000353801.7	c.-77T>A		5_prime_UTR_variant	1/12	1		ENSP00000325875	P1
HSP90AB1	ENST00000620073.4	c.-1+788T>A		intron_variant		5		ENSP00000481908	P1

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4839 AN: 152002 Hom.: 119 Cov.: 32

Gnomad AFR AF: 0.00883

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0332

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0490

Gnomad OTH AF: 0.0268

GnomAD4 exome AF: 0.0441 AC: 3 AN: 68 Hom.: 0 Cov.: 0 AF XY: 0.0208 AC XY: 1 AN XY: 48

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0400

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0318 AC: 4839 AN: 152120 Hom.: 119 Cov.: 32 AF XY: 0.0304 AC XY: 2257 AN XY: 74348

Gnomad4 AFR AF: 0.00881

Gnomad4 AMR AF: 0.0151

Gnomad4 ASJ AF: 0.0332

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0154

Gnomad4 FIN AF: 0.0573

Gnomad4 NFE AF: 0.0490

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0155 Hom.: 9

Bravo AF: 0.0282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.024
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs35074133; hg19: chr6-44214869;