rs10493148

Positions:

• chr4-127830446-T-C
• chr4-127830446-T-G

Variant summary

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

The NM_014278.4(HSPA4L):​c.2167-192T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 152,294 control chromosomes in the GnomAD database, including 298 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 0.030 (298 hom., 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA4L	NM_014278.4	c.2167-192T>C		intron_variant		ENST00000296464.9
HSPA4L	NM_001317381.2	c.2260-192T>C		intron_variant
HSPA4L	NM_001317382.2	c.2089-192T>C		intron_variant
HSPA4L	NM_001317383.2	c.2044-192T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA4L	ENST00000296464.9	c.2167-192T>C		intron_variant		1	NM_014278.4	P1
HSPA4L	ENST00000505726.1	c.2089-192T>C		intron_variant		2
HSPA4L	ENST00000508776.5	c.2167-192T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4617 AN: 152176 Hom.: 299 Cov.: 32

Gnomad AFR AF: 0.00367

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0302

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

GnomAD4 genome AF: 0.0303 AC: 4612 AN: 152294 Hom.: 298 Cov.: 32 AF XY: 0.0346 AC XY: 2574 AN XY: 74448

Gnomad4 AFR AF: 0.00366

Gnomad4 AMR AF: 0.0880

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.0176

Gnomad4 FIN AF: 0.0605

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.0285

Alfa AF: 0.0302 Hom.: 42

Bravo AF: 0.0346

Asia WGS AF: 0.127 AC: 440 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.6
DANN	Benign	0.80

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;