chr6-31827773-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005346.6(HSPA1B):​c.-178C>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 0.000000808 in 1,237,052 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: HSPA1B NM_005346.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.018).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA1B	NM_005346.6	MANE Select	c.-178C>A		5_prime_UTR	Exon 1 of 1	NP_005337.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA1B	ENST00000375650.5	TSL:6 MANE Select	c.-178C>A		5_prime_UTR	Exon 1 of 1	ENSP00000364801.3
	SNHG32	ENST00000718216.1		n.364+415C>A		intron	N/A
	SNHG32	ENST00000718219.1		n.184+5472C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.08e-7 AC: 1 AN: 1237052 Hom.: 0 Cov.: 20 AF XY: 0.00000162 AC XY: 1 AN XY: 617636

African (AFR) AF: 0.00 AC: 0 AN: 28542

American (AMR) AF: 0.00 AC: 0 AN: 35438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24008

East Asian (EAS) AF: 0.00 AC: 0 AN: 35054

South Asian (SAS) AF: 0.00 AC: 0 AN: 76346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5408

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 938876

Other (OTH) AF: 0.00 AC: 0 AN: 52790

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.20
DANN	Benign	0.53
PhyloP100		-2.0
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1

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;