rs33934112

chr6-31815599-C-Achr6-31815599-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_005345.6(HSPA1A):c.-158C>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 0.0107 in 1,552,412 control chromosomes in the GnomAD database, including 164 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 0.0087 (7 hom., cov: 32)
  • Exomes 𝑓: 0.011 (157 hom.)
• Consequence: HSPA1A NM_005345.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100

Genes affected

HSPA1A (HGNC:5232): (heat shock protein family A (Hsp70) member 1A) 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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00867 (1321/152346) while in subpopulation SAS AF= 0.0348 (168/4828). AF 95% confidence interval is 0.0305. There are 7 homozygotes in gnomad4. There are 694 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1320 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA1A	NM_005345.6	c.-158C>A		5_prime_UTR_variant	1/1	ENST00000375651.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA1A	ENST00000375651.7	c.-158C>A		5_prime_UTR_variant	1/1		NM_005345.6	P1
HSPA1A	ENST00000608703.1	c.-158C>A		5_prime_UTR_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.00867 AC: 1320 AN: 152228 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00369

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.00885

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00999

Gnomad OTH AF: 0.00716

GnomAD4 exome AF: 0.0109 AC: 15293 AN: 1400066 Hom.: 157 Cov.: 26 AF XY: 0.0120 AC XY: 8345 AN XY: 696830

Gnomad4 AFR exome AF: 0.00318

Gnomad4 AMR exome AF: 0.00479

Gnomad4 ASJ exome AF: 0.00820

Gnomad4 EAS exome AF: 0.00660

Gnomad4 SAS exome AF: 0.0383

Gnomad4 FIN exome AF: 0.00959

Gnomad4 NFE exome AF: 0.00944

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.00867 AC: 1321 AN: 152346 Hom.: 7 Cov.: 32 AF XY: 0.00932 AC XY: 694 AN XY: 74500

Gnomad4 AFR AF: 0.00368

Gnomad4 AMR AF: 0.00810

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.0102

Gnomad4 SAS AF: 0.0348

Gnomad4 FIN AF: 0.00885

Gnomad4 NFE AF: 0.0100

Gnomad4 OTH AF: 0.00709

Alfa AF: 0.00290 Hom.: 0

Bravo AF: 0.00770

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	4.2
Dann	Benign	0.56
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

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: rs33934112; hg19: chr6-31783376;