rs11557922

Positions:

• chr6-31815660-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005345.6(HSPA1A):​c.-97T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 1,612,906 control chromosomes in the GnomAD database, including 543 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 0.028 (84 hom., cov: 32)
  • Exomes 𝑓: 0.022 (459 hom.)
• Consequence: HSPA1A NM_005345.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0282 (4299/152354) while in subpopulation AMR AF= 0.0487 (745/15304). AF 95% confidence interval is 0.0458. There are 84 homozygotes in gnomad4. There are 2057 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4299 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA1A	NM_005345.6	c.-97T>C		5_prime_UTR_variant	1/1	ENST00000375651.7	NP_005336.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA1A	ENST00000375651.7	c.-97T>C		5_prime_UTR_variant	1/1	6	NM_005345.6	ENSP00000364802.5
HSPA1A	ENST00000608703.1	c.-97T>C		5_prime_UTR_variant	1/2	2		ENSP00000477378.1

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4309 AN: 152236 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.0449

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.00282

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0223

Gnomad OTH AF: 0.0392

GnomAD4 exome AF: 0.0216 AC: 31621 AN: 1460552 Hom.: 459 Cov.: 31 AF XY: 0.0214 AC XY: 15563 AN XY: 726588

Gnomad4 AFR exome AF: 0.0428

Gnomad4 AMR exome AF: 0.0339

Gnomad4 ASJ exome AF: 0.0461

Gnomad4 EAS exome AF: 0.00383

Gnomad4 SAS exome AF: 0.0167

Gnomad4 FIN exome AF: 0.00334

Gnomad4 NFE exome AF: 0.0216

Gnomad4 OTH exome AF: 0.0234

GnomAD4 genome AF: 0.0282 AC: 4299 AN: 152354 Hom.: 84 Cov.: 32 AF XY: 0.0276 AC XY: 2057 AN XY: 74504

Gnomad4 AFR AF: 0.0393

Gnomad4 AMR AF: 0.0487

Gnomad4 ASJ AF: 0.0449

Gnomad4 EAS AF: 0.00945

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.00282

Gnomad4 NFE AF: 0.0223

Gnomad4 OTH AF: 0.0383

Alfa AF: 0.0243 Hom.: 34

Bravo AF: 0.0330

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.7
DANN	Benign	0.64

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: rs11557922; hg19: chr6-31783437;