NM_001317100.2:c.73C>T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PVS1_StrongBP6BS1BS2

The NM_001317100.2(DNAJB4):c.73C>T(p.Arg25*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 152,066 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.010 ( 33 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAJB4
NM_001317100.2 stop_gained

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.44

Variant links:

Genes affected

DNAJB4 (HGNC:14886): (DnaJ heat shock protein family (Hsp40) member B4) The protein encoded by this gene is a molecular chaperone, tumor suppressor, and member of the heat shock protein-40 family. The encoded protein binds the cell adhesion protein E-cadherin and targets it to the plasma membrane. This protein also binds incorrectly folded E-cadherin and targets it for endoplasmic reticulum-associated degradation. This gene is a strong tumor suppressor for colorectal carcinoma, and downregulation of it may serve as a good biomarker for predicting patient outcomes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

DNAJB4 links:

GIPC2 (HGNC:18177): (GIPC PDZ domain containing family member 2) Enables identical protein binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

GIPC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.

BP6

Variant 1-77992848-C-T is Benign according to our data. Variant chr1-77992848-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3039041.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1543/152066) while in subpopulation AFR AF= 0.0354 (1467/41488). AF 95% confidence interval is 0.0339. There are 33 homozygotes in gnomad4. There are 723 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
DNAJB4	NM_001317100.2 link	c.73C>T	p.Arg25*	stop_gained	Exon 2 of 4	NP_001304029.1	Q9UDY4
DNAJB4	NM_001317099.2 link	c.-31-12232C>T		intron_variant	Intron 1 of 3	NP_001304028.1	Q9UDY4
DNAJB4	NM_001317101.2 link	c.-135+13229C>T		intron_variant	Intron 1 of 2	NP_001304030.1	Q9UDY4B4DNN2
DNAJB4	NM_001317102.2 link	c.-135+13555C>T		intron_variant	Intron 1 of 2	NP_001304031.1	Q9UDY4B4DNN2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
DNAJB4	ENST00000426517.1 link	c.-31-12232C>T	intron_variant	Intron 1 of 2	3	ENSP00000399494.1	C9JUL4
DNAJB4	ENST00000477671.2 link	n.255C>T	non_coding_transcript_exon_variant	Exon 3 of 4	5
GIPC2	ENST00000476882.1 link	n.78+13229C>T	intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1544

AN:

151948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0355

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00348

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00576

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

104

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0101

AC:

1543

AN:

152066

Hom.:

Cov.:

AF XY:

0.00972

AC XY:

723

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0354

Gnomad4 AMR

AF:

0.00347

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00570

Alfa

AF:

0.00770

Hom.:

Bravo

AF:

0.0112

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DNAJB4-related disorder

Benign:1

Feb 27, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.32

DANN

Benign

0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over