NM_001317100.2:c.73C>T

Variant names:

• chr1-77992848-C-T
• rs149535846
• ENST00000939132.1:c.-50C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

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
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.44
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• 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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317100.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB4	NM_001317100.2		c.73C>T	p.Arg25*	stop_gained	Exon 2 of 4	NP_001304029.1
	DNAJB4	NM_001317099.2		c.-31-12232C>T		intron	N/A	NP_001304028.1	Q9UDY4
	DNAJB4	NM_001317101.2		c.-135+13229C>T		intron	N/A	NP_001304030.1	B4DNN2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB4	ENST00000939132.1		c.-50C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000609191.1
	DNAJB4	ENST00000939136.1		c.-50C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000609195.1
	DNAJB4	ENST00000957220.1		c.-50C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000627279.1

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1544 AN: 151948 Hom.: 33 Cov.: 32

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: 0 AN: 104 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 78

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 84

Other (OTH) AF: 0.00 AC: 0 AN: 10

GnomAD4 genome AF: 0.0101 AC: 1543 AN: 152066 Hom.: 33 Cov.: 32 AF XY: 0.00972 AC XY: 723 AN XY: 74352

African (AFR) AF: 0.0354 AC: 1467 AN: 41488

American (AMR) AF: 0.00347 AC: 53 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67964

Other (OTH) AF: 0.00570 AC: 12 AN: 2104

Alfa AF: 0.00770 Hom.: 3

Bravo AF: 0.0112

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DNAJB4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.32
DANN	Benign	0.78
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs149535846; hg19: chr1-78458532;