rs14355

Positions:

• chr5-133104593-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000304858.7(HSPA4):​c.*157C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 629,318 control chromosomes in the GnomAD database, including 21,034 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 0.26 (5417 hom., cov: 32)
  • Exomes 𝑓: 0.25 (15617 hom.)
• Consequence: HSPA4 ENST00000304858.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24

Genes affected

HSPA4 (HGNC:5237): (heat shock protein family A (Hsp70) member 4) Predicted to enable ATP binding activity. Involved in chaperone-mediated protein complex assembly and protein insertion into mitochondrial outer membrane. Located in cytosol and extracellular exosome. Implicated in Chagas disease. Biomarker of chronic obstructive pulmonary disease; rheumatoid arthritis; type 2 diabetes mellitus; and ulcerative colitis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA4	NM_002154.4	c.*157C>G		3_prime_UTR_variant	19/19	ENST00000304858.7	NP_002145.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA4	ENST00000304858.7	c.*157C>G		3_prime_UTR_variant	19/19	1	NM_002154.4	ENSP00000302961	P1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39588 AN: 151994 Hom.: 5406 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.250 AC: 119300 AN: 477206 Hom.: 15617 Cov.: 5 AF XY: 0.252 AC XY: 63131 AN XY: 251016

Gnomad4 AFR exome AF: 0.307

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.261 AC: 39639 AN: 152112 Hom.: 5417 Cov.: 32 AF XY: 0.261 AC XY: 19377 AN XY: 74364

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.250

Alfa AF: 0.265 Hom.: 703

Bravo AF: 0.251

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs14355; hg19: chr5-132440285;