4-127830446-T-G

Position:

• chr4-127830446-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014278.4(HSPA4L):​c.2167-192T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: HSPA4L NM_014278.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

Genes affected

HSPA4L (HGNC:17041): (heat shock protein family A (Hsp70) member 4 like) The protein encoded by this gene is heat shock inducible and may act as a chaperone. The encoded protein can protect the heat-shocked cell against the harmful effects of aggregated proteins. This gene is highly expressed in leukemia cells and may be a good target for therapeutic intervention. Several transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA4L	NM_014278.4	c.2167-192T>G		intron_variant		ENST00000296464.9	NP_055093.2
HSPA4L	NM_001317381.2	c.2260-192T>G		intron_variant			NP_001304310.1
HSPA4L	NM_001317382.2	c.2089-192T>G		intron_variant			NP_001304311.1
HSPA4L	NM_001317383.2	c.2044-192T>G		intron_variant			NP_001304312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA4L	ENST00000296464.9	c.2167-192T>G		intron_variant		1	NM_014278.4	ENSP00000296464.3
HSPA4L	ENST00000508776.5	c.2167-192T>G		intron_variant		2		ENSP00000422482.1
HSPA4L	ENST00000505726.1	c.2089-192T>G		intron_variant		2		ENSP00000425645.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.8
DANN	Benign	0.77

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: rs10493148; hg19: chr4-128751601;