rs11162405

chr1-78003976-A-G

Variant summary

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

The NM_001317099.2(DNAJB4):c.-31-1104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,086 control chromosomes in the GnomAD database, including 10,927 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 0.37 (10927 hom., cov: 32)
• Consequence: DNAJB4 NM_001317099.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB4	NM_001317099.2	c.-31-1104A>G		intron_variant
DNAJB4	NM_001317100.2	c.92-9075A>G		intron_variant
DNAJB4	NM_001317101.2	c.-134-9075A>G		intron_variant
DNAJB4	NM_001317102.2	c.-134-9075A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB4	ENST00000426517.1	c.-31-1104A>G		intron_variant		3
GIPC2	ENST00000476882.1	n.78+24357A>G		intron_variant, non_coding_transcript_variant		3
DNAJB4	ENST00000477671.2	n.274-9075A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56950 AN: 151970 Hom.: 10930 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.375 AC: 56962 AN: 152086 Hom.: 10927 Cov.: 32 AF XY: 0.372 AC XY: 27637 AN XY: 74356

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.414

Alfa AF: 0.404 Hom.: 14417

Bravo AF: 0.373

Asia WGS AF: 0.430 AC: 1495 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	7.9
Dann	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11162405; hg19: chr1-78469660;