6-31829660-T-G

Variant names:

• chr6-31829660-T-G
• rs35682610
• NM_005346.6:c.1710T>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_005346.6(HSPA1B):​c.1710T>G​(p.Val570Val) 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
• Publications: 4 publications found

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]

SNHG32 (HGNC:19078): (small nucleolar RNA host gene 32) Predicted to enable double-stranded RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005346.6. 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
	HSPA1B	NM_005346.6	MANE Select	c.1710T>G	p.Val570Val	synonymous	Exon 1 of 1	NP_005337.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA1B	ENST00000375650.5	TSL:6 MANE Select	c.1710T>G	p.Val570Val	synonymous	Exon 1 of 1	ENSP00000364801.3
	SNHG32	ENST00000649802.1		n.827T>G		non_coding_transcript_exon	Exon 1 of 4
	SNHG32	ENST00000718216.1		n.364+2302T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2434 AN: 151066 Hom.: 17 Cov.: 23

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

GnomAD2 exomes AF: 0.000901 AC: 218 AN: 242016 AF XY: 0.000894

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00748 AC: 245 AN: 32738

American (AMR) AF: 0.00374 AC: 165 AN: 44088

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 287 AN: 25624

East Asian (EAS) AF: 0.0211 AC: 816 AN: 38700

South Asian (SAS) AF: 0.00189 AC: 159 AN: 83914

European-Finnish (FIN) AF: 0.00253 AC: 132 AN: 52098

Middle Eastern (MID) AF: 0.00335 AC: 19 AN: 5670

European-Non Finnish (NFE) AF: 0.00207 AC: 2279 AN: 1101452

Other (OTH) AF: 0.00495 AC: 296 AN: 59740

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0262 AC: 1078 AN: 41072

American (AMR) AF: 0.0138 AC: 209 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.0230 AC: 79 AN: 3442

East Asian (EAS) AF: 0.0244 AC: 125 AN: 5120

South Asian (SAS) AF: 0.0157 AC: 75 AN: 4784

European-Finnish (FIN) AF: 0.00490 AC: 52 AN: 10608

Middle Eastern (MID) AF: 0.0241 AC: 7 AN: 290

European-Non Finnish (NFE) AF: 0.0114 AC: 772 AN: 67672

Other (OTH) AF: 0.0167 AC: 35 AN: 2102

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0128 Hom.: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.0
DANN	Benign	0.75
PhyloP100		0.042
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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