rs10493148

Variant names:

• chr4-127830446-T-C
• rs10493148
• NM_014278.4:c.2167-192T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ENSG00000295993 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HSPA4L	NM_014278.4	c.2167-192T>C		intron_variant	Intron 17 of 18	ENST00000296464.9	NP_055093.2
HSPA4L	NM_001317381.2	c.2260-192T>C		intron_variant	Intron 18 of 19		NP_001304310.1
HSPA4L	NM_001317382.2	c.2089-192T>C		intron_variant	Intron 17 of 18		NP_001304311.1
HSPA4L	NM_001317383.2	c.2044-192T>C		intron_variant	Intron 16 of 17		NP_001304312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA4L	ENST00000296464.9	c.2167-192T>C		intron_variant	Intron 17 of 18	1	NM_014278.4	ENSP00000296464.3

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

African (AFR) AF: 0.00366 AC: 152 AN: 41578

American (AMR) AF: 0.0880 AC: 1346 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3468

East Asian (EAS) AF: 0.262 AC: 1358 AN: 5174

South Asian (SAS) AF: 0.0176 AC: 85 AN: 4824

European-Finnish (FIN) AF: 0.0605 AC: 642 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 945 AN: 68038

Other (OTH) AF: 0.0285 AC: 60 AN: 2108

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
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs10493148; hg19: chr4-128751601;