4-99941725-T-C

Variant names:

• chr4-99941725-T-C
• rs6854536
• NM_001031723.4:c.133+4714A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031723.4(DNAJB14):​c.133+4714A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,942 control chromosomes in the GnomAD database, including 16,361 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 0.45 (16361 hom., cov: 32)
• Consequence: DNAJB14 NM_001031723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB14	NM_001031723.4	c.133+4714A>G		intron_variant	Intron 1 of 7	ENST00000442697.7	NP_001026893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB14	ENST00000442697.7	c.133+4714A>G		intron_variant	Intron 1 of 7	1	NM_001031723.4	ENSP00000404381.2

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68021 AN: 151824 Hom.: 16328 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.448 AC: 68097 AN: 151942 Hom.: 16361 Cov.: 32 AF XY: 0.444 AC XY: 32975 AN XY: 74264

African (AFR) AF: 0.629 AC: 26057 AN: 41426

American (AMR) AF: 0.396 AC: 6047 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1650 AN: 3466

East Asian (EAS) AF: 0.392 AC: 2028 AN: 5168

South Asian (SAS) AF: 0.374 AC: 1807 AN: 4826

European-Finnish (FIN) AF: 0.402 AC: 4249 AN: 10562

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.365 AC: 24769 AN: 67890

Other (OTH) AF: 0.453 AC: 957 AN: 2114

Alfa AF: 0.407 Hom.: 1665

Bravo AF: 0.458

Asia WGS AF: 0.413 AC: 1436 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.4
DANN	Benign	0.40
PhyloP100		-0.45
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: rs6854536; hg19: chr4-100862882;