4-99943207-G-A

Position:

• chr4-99943207-G-A

Variant summary

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

The NM_001031723.4(DNAJB14):​c.133+3232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0648 in 152,138 control chromosomes in the GnomAD database, including 463 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 0.065 (463 hom., cov: 32)
• Consequence: DNAJB14 NM_001031723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

Genes affected

DNAJB14 (HGNC:25881): (DnaJ heat shock protein family (Hsp40) member B14) Enables Hsp70 protein binding activity. Involved in cellular protein-containing complex assembly and chaperone cofactor-dependent protein refolding. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB14	NM_001031723.4	c.133+3232C>T		intron_variant		ENST00000442697.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB14	ENST00000442697.7	c.133+3232C>T		intron_variant		1	NM_001031723.4	P1

Frequencies

GnomAD3 genomes AF: 0.0649 AC: 9869 AN: 152020 Hom.: 463 Cov.: 32

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0899

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.0876

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0483

Gnomad OTH AF: 0.0647

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

GnomAD4 genome AF: 0.0648 AC: 9866 AN: 152138 Hom.: 463 Cov.: 32 AF XY: 0.0692 AC XY: 5146 AN XY: 74354

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.0898

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.0870

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0483

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0566 Hom.: 89

Bravo AF: 0.0643

Asia WGS AF: 0.179 AC: 621 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.39

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: rs10014424; hg19: chr4-100864364;