rs14355

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-133104593-C-A
• chr5-133104593-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002154.4(HSPA4):​c.*157C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 477,788 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: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HSPA4 NM_002154.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA4	NM_002154.4	c.*157C>A		3_prime_UTR_variant	Exon 19 of 19	ENST00000304858.7	NP_002145.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA4	ENST00000304858.7	c.*157C>A		3_prime_UTR_variant	Exon 19 of 19	1	NM_002154.4	ENSP00000302961.2
HSPA4	ENST00000514825.1	n.*116C>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000209 AC: 1 AN: 477788 Hom.: 0 Cov.: 5 AF XY: 0.00000398 AC XY: 1 AN XY: 251330

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 12726

American (AMR) AF: 0.00 AC: 0 AN: 18366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13850

East Asian (EAS) AF: 0.00 AC: 0 AN: 30916

South Asian (SAS) AF: 0.00 AC: 0 AN: 45230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2016

European-Non Finnish (NFE) AF: 0.00000341 AC: 1 AN: 292840

Other (OTH) AF: 0.00 AC: 0 AN: 26714

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		2.2

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

Other links and lift over

dbSNP: rs14355; hg19: chr5-132440285;