chr6-31829660-T-G

Position:

• chr6-31829660-T-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_005346.6(HSPA1B):​c.1710T>G​(p.Val570=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.016 (17 hom., cov: 23)
  • Exomes 𝑓: 0.0030 (196 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSPA1B NM_005346.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

Genes affected

HSPA1B (HGNC:5233): (heat shock protein family A (Hsp70) member 1B) This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=0.042 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA1B	NM_005346.6	c.1710T>G	p.Val570=	synonymous_variant	1/1	ENST00000375650.5	NP_005337.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA1B	ENST00000375650.5	c.1710T>G	p.Val570=	synonymous_variant	1/1		NM_005346.6	ENSP00000364801	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2434 AN: 151066 Hom.: 17 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.0244

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.0192

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.0168

GnomAD3 exomes AF: 0.000901 AC: 218 AN: 242016 Hom.: 40 AF XY: 0.000894 AC XY: 118 AN XY: 131960

Gnomad AFR exome AF: 0.00220

Gnomad AMR exome AF: 0.000472

Gnomad ASJ exome AF: 0.00123

Gnomad EAS exome AF: 0.00166

Gnomad SAS exome AF: 0.00151

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000725

Gnomad OTH exome AF: 0.000167

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00305 AC: 4398 AN: 1444024 Hom.: 196 Cov.: 31 AF XY: 0.00310 AC XY: 2228 AN XY: 718082

Gnomad4 AFR exome AF: 0.00748

Gnomad4 AMR exome AF: 0.00374

Gnomad4 ASJ exome AF: 0.0112

Gnomad4 EAS exome AF: 0.0211

Gnomad4 SAS exome AF: 0.00189

Gnomad4 FIN exome AF: 0.00253

Gnomad4 NFE exome AF: 0.00207

Gnomad4 OTH exome AF: 0.00495

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0161 AC: 2436 AN: 151184 Hom.: 17 Cov.: 23 AF XY: 0.0156 AC XY: 1156 AN XY: 73934

Gnomad4 AFR AF: 0.0262

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.0230

Gnomad4 EAS AF: 0.0244

Gnomad4 SAS AF: 0.0157

Gnomad4 FIN AF: 0.00490

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.0167

Alfa AF: 0.0124 Hom.: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.0
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs35682610; hg19: chr6-31797437; COSMIC: COSV65128261; COSMIC: COSV65128261;