rs142025971

chr15-78266242-CAT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000446172.2(DNAJA4):c.1_2del(p.Met1?) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0369 in 1,613,698 control chromosomes in the GnomAD database, including 1,349 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (92 hom., cov: 33)
  • Exomes 𝑓: 0.038 (1257 hom.)
• Consequence: DNAJA4 ENST00000446172.2 frameshift, start_lost
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.141

Genes affected

DNAJA4 (HGNC:14885): (DnaJ heat shock protein family (Hsp40) member A4) Enables chaperone binding activity and unfolded protein binding activity. Involved in several processes, including negative regulation of endothelial cell migration; negative regulation of inclusion body assembly; and protein refolding. Located in cytosol and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-78266242-CAT-C is Benign according to our data. Variant chr15-78266242-CAT-C is described in ClinVar as [Likely_benign]. Clinvar id is 402789.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJA4	NM_001130182.2	c.132+1348_132+1349del		intron_variant		ENST00000394852.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJA4	ENST00000394852.8	c.132+1348_132+1349del		intron_variant		1	NM_001130182.2	P1

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4498 AN: 152182 Hom.: 92 Cov.: 33

Gnomad AFR AF: 0.00668

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.0396

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0436

Gnomad OTH AF: 0.0401

GnomAD3 exomes AF: 0.0323 AC: 8027 AN: 248720 Hom.: 200 AF XY: 0.0332 AC XY: 4484 AN XY: 135162

Gnomad AFR exome AF: 0.00603

Gnomad AMR exome AF: 0.0228

Gnomad ASJ exome AF: 0.0602

Gnomad EAS exome AF: 0.000223

Gnomad SAS exome AF: 0.0102

Gnomad FIN exome AF: 0.0359

Gnomad NFE exome AF: 0.0464

Gnomad OTH exome AF: 0.0383

GnomAD4 exome AF: 0.0377 AC: 55083 AN: 1461398 Hom.: 1257 AF XY: 0.0373 AC XY: 27096 AN XY: 726988

Gnomad4 AFR exome AF: 0.00687

Gnomad4 AMR exome AF: 0.0242

Gnomad4 ASJ exome AF: 0.0588

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.0101

Gnomad4 FIN exome AF: 0.0354

Gnomad4 NFE exome AF: 0.0422

Gnomad4 OTH exome AF: 0.0352

GnomAD4 genome AF: 0.0295 AC: 4498 AN: 152300 Hom.: 92 Cov.: 33 AF XY: 0.0286 AC XY: 2126 AN XY: 74464

Gnomad4 AFR AF: 0.00666

Gnomad4 AMR AF: 0.0306

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00850

Gnomad4 FIN AF: 0.0396

Gnomad4 NFE AF: 0.0436

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0125 Hom.: 26

Bravo AF: 0.0292

Asia WGS AF: 0.00664 AC: 25 AN: 3478

EpiCase AF: 0.0514

EpiControl AF: 0.0510

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes:63/2178=2.89% -

Computational scores

Source: dbNSFP v4.3

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: rs142025971; hg19: chr15-78558584;