rs17268499

Positions:

• chr10-14866572-C-T

Variant summary

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

The NM_016299.4(HSPA14):​c.994-511C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,040 control chromosomes in the GnomAD database, including 1,219 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 0.12 (1219 hom., cov: 32)
• Consequence: HSPA14 NM_016299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280

Genes affected

HSPA14 (HGNC:29526): (heat shock protein family A (Hsp70) member 14) Predicted to enable several functions, including ATP binding activity; misfolded protein binding activity; and unfolded protein binding activity. Predicted to be involved in several processes, including cellular response to unfolded protein; chaperone cofactor-dependent protein refolding; and protein refolding. Located in cytosol. Colocalizes with ribosome. [provided by Alliance of Genome Resources, Apr 2022]

LOC124902382 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA14	NM_016299.4	c.994-511C>T		intron_variant		ENST00000378372.8	NP_057383.2
LOC124902382	XR_007062064.1	n.393-183G>A		intron_variant, non_coding_transcript_variant
LOC124902382	XR_007062065.1	n.487G>A		non_coding_transcript_exon_variant	3/3
LOC124902382	XR_007062066.1	n.393-422G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA14	ENST00000378372.8	c.994-511C>T		intron_variant		1	NM_016299.4	ENSP00000367623	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18123 AN: 151922 Hom.: 1219 Cov.: 32

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.00557

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.119 AC: 18131 AN: 152040 Hom.: 1219 Cov.: 32 AF XY: 0.119 AC XY: 8847 AN XY: 74310

Gnomad4 AFR AF: 0.0730

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0988

Gnomad4 EAS AF: 0.00578

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.116

Alfa AF: 0.144 Hom.: 688

Bravo AF: 0.113

Asia WGS AF: 0.0620 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.33

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: rs17268499; hg19: chr10-14908571;