chr5-133104593-C-G

Variant names:

• chr5-133104593-C-G
• rs14355
• NM_002154.4:c.*157C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002154.4(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 NM_002154.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002154.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA4	NM_002154.4	MANE Select	c.*157C>G		3_prime_UTR	Exon 19 of 19	NP_002145.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA4	ENST00000304858.7	TSL:1 MANE Select	c.*157C>G		3_prime_UTR	Exon 19 of 19	ENSP00000302961.2
	HSPA4	ENST00000514825.1	TSL:2	n.*116C>G		downstream_gene	N/A

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

African (AFR) AF: 0.307 AC: 3897 AN: 12712

American (AMR) AF: 0.160 AC: 2940 AN: 18344

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 3592 AN: 13834

East Asian (EAS) AF: 0.102 AC: 3149 AN: 30896

South Asian (SAS) AF: 0.267 AC: 12074 AN: 45176

European-Finnish (FIN) AF: 0.283 AC: 9920 AN: 35072

Middle Eastern (MID) AF: 0.276 AC: 555 AN: 2014

European-Non Finnish (NFE) AF: 0.262 AC: 76503 AN: 292472

Other (OTH) AF: 0.250 AC: 6670 AN: 26686

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

African (AFR) AF: 0.309 AC: 12840 AN: 41492

American (AMR) AF: 0.173 AC: 2651 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 883 AN: 3466

East Asian (EAS) AF: 0.113 AC: 585 AN: 5184

South Asian (SAS) AF: 0.257 AC: 1242 AN: 4824

European-Finnish (FIN) AF: 0.289 AC: 3053 AN: 10568

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17503 AN: 67978

Other (OTH) AF: 0.250 AC: 529 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.81
PhyloP100		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism

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: rs14355; hg19: chr5-132440285;