rs539689

Positions:

• chr6-31829810-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005346.6(HSPA1B):​c.1860C>G​(p.Gly620Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,050 control chromosomes in the GnomAD database, including 21,143 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 0.52 (21143 hom., cov: 27)
  • Exomes 𝑓: 0.51 (195339 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSPA1B NM_005346.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.52

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]

ENSG00000285565 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-3.52 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA1B	NM_005346.6	c.1860C>G	p.Gly620Gly	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.1860C>G	p.Gly620Gly	synonymous_variant	1/1	6	NM_005346.6	ENSP00000364801.3
ENSG00000285565	ENST00000649802.1	n.920+57C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.523 AC: 78891 AN: 150932 Hom.: 21120 Cov.: 27

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.542

GnomAD3 exomes AF: 0.574 AC: 125453 AN: 218688 Hom.: 41028 AF XY: 0.576 AC XY: 68486 AN XY: 118948

Gnomad AFR exome AF: 0.444

Gnomad AMR exome AF: 0.712

Gnomad ASJ exome AF: 0.635

Gnomad EAS exome AF: 0.617

Gnomad SAS exome AF: 0.660

Gnomad FIN exome AF: 0.628

Gnomad NFE exome AF: 0.508

Gnomad OTH exome AF: 0.564

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.511 AC: 670450 AN: 1313160 Hom.: 195339 Cov.: 61 AF XY: 0.516 AC XY: 337559 AN XY: 653738

Gnomad4 AFR exome AF: 0.440

Gnomad4 AMR exome AF: 0.705

Gnomad4 ASJ exome AF: 0.621

Gnomad4 EAS exome AF: 0.702

Gnomad4 SAS exome AF: 0.652

Gnomad4 FIN exome AF: 0.616

Gnomad4 NFE exome AF: 0.478

Gnomad4 OTH exome AF: 0.514

GnomAD4 genome AF: 0.523 AC: 78955 AN: 151050 Hom.: 21143 Cov.: 27 AF XY: 0.533 AC XY: 39280 AN XY: 73716

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.546

Alfa AF: 0.521 Hom.: 3965

Bravo AF: 0.519

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.40
DANN	Benign	0.70

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: rs539689; hg19: chr6-31797587; COSMIC: COSV65128330; COSMIC: COSV65128330;