6-31827773-C-T

Variant names:

• chr6-31827773-C-T
• rs6457452
• NM_005346.6:c.-178C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005346.6(HSPA1B):​c.-178C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 1,388,778 control chromosomes in the GnomAD database, including 5,920 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.11 (1208 hom., cov: 31)
  • Exomes 𝑓: 0.072 (4712 hom.)
• Consequence: HSPA1B NM_005346.6 5_prime_UTR
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -2.05
• Publications: 40 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.017).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA1B	NM_005346.6	c.-178C>T		5_prime_UTR_variant	Exon 1 of 1	ENST00000375650.5	NP_005337.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA1B	ENST00000375650.5	c.-178C>T		5_prime_UTR_variant	Exon 1 of 1	6	NM_005346.6	ENSP00000364801.3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16169 AN: 152052 Hom.: 1202 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0615

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0387

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0675

Gnomad OTH AF: 0.143

GnomAD2 exomes AF: 0.0934 AC: 13246 AN: 141746 AF XY: 0.0939

Gnomad AFR exome AF: 0.194

Gnomad AMR exome AF: 0.0907

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.0505

Gnomad FIN exome AF: 0.0381

Gnomad NFE exome AF: 0.0688

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.0722 AC: 89239 AN: 1236608 Hom.: 4712 Cov.: 20 AF XY: 0.0740 AC XY: 45688 AN XY: 617416

African (AFR) AF: 0.193 AC: 5511 AN: 28520

American (AMR) AF: 0.0953 AC: 3377 AN: 35438

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 4083 AN: 24004

East Asian (EAS) AF: 0.0684 AC: 2398 AN: 35054

South Asian (SAS) AF: 0.133 AC: 10128 AN: 76332

European-Finnish (FIN) AF: 0.0372 AC: 1511 AN: 40590

Middle Eastern (MID) AF: 0.131 AC: 707 AN: 5408

European-Non Finnish (NFE) AF: 0.0602 AC: 56531 AN: 938498

Other (OTH) AF: 0.0946 AC: 4993 AN: 52764

GnomAD4 genome AF: 0.106 AC: 16191 AN: 152170 Hom.: 1208 Cov.: 31 AF XY: 0.105 AC XY: 7840 AN XY: 74388

African (AFR) AF: 0.186 AC: 7701 AN: 41490

American (AMR) AF: 0.106 AC: 1625 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 574 AN: 3468

East Asian (EAS) AF: 0.0617 AC: 320 AN: 5188

South Asian (SAS) AF: 0.126 AC: 609 AN: 4828

European-Finnish (FIN) AF: 0.0387 AC: 411 AN: 10616

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0675 AC: 4587 AN: 67988

Other (OTH) AF: 0.146 AC: 308 AN: 2110

Alfa AF: 0.0807 Hom.: 2487

Bravo AF: 0.117

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Chronic obstructive pulmonary disease Other:1

Aug 04, 2019

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.25
DANN	Benign	0.83
PhyloP100		-2.0
PromoterAI		0.035	Neutral
Mutation Taster		=300/0	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: rs6457452; hg19: chr6-31795550;