rs142025971

Variant names:

• chr15-78266242-CAT-C
• rs142025971
• ENST00000446172.2:c.1_2delAT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000446172.2(DNAJA4):​c.1_2delAT​(p.Met1fs) 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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000446172.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJA4	NM_001130182.2	MANE Select	c.132+1348_132+1349delAT		intron	N/A	NP_001123654.1
	DNAJA4	NM_001130183.2		c.1_2delAT	p.Met1fs	frameshift start_lost	Exon 1 of 7	NP_001123655.1
	DNAJA4	NM_018602.4		c.219+1348_219+1349delAT		intron	N/A	NP_061072.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJA4	ENST00000446172.2	TSL:1	c.1_2delAT	p.Met1fs	frameshift start_lost	Exon 1 of 7	ENSP00000413499.2
	DNAJA4	ENST00000394852.8	TSL:1 MANE Select	c.132+1348_132+1349delAT		intron	N/A	ENSP00000378321.3
	DNAJA4	ENST00000394855.7	TSL:1	c.219+1348_219+1349delAT		intron	N/A	ENSP00000378324.3

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

GnomAD2 exomes AF: 0.0323 AC: 8027 AN: 248720 AF XY: 0.0332

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 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

African (AFR) AF: 0.00687 AC: 230 AN: 33480

American (AMR) AF: 0.0242 AC: 1084 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 1536 AN: 26126

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39694

South Asian (SAS) AF: 0.0101 AC: 873 AN: 86240

European-Finnish (FIN) AF: 0.0354 AC: 1892 AN: 53388

Middle Eastern (MID) AF: 0.0758 AC: 437 AN: 5768

European-Non Finnish (NFE) AF: 0.0422 AC: 46898 AN: 1111622

Other (OTH) AF: 0.0352 AC: 2127 AN: 60368

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

African (AFR) AF: 0.00666 AC: 277 AN: 41570

American (AMR) AF: 0.0306 AC: 468 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00850 AC: 41 AN: 4824

European-Finnish (FIN) AF: 0.0396 AC: 420 AN: 10604

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0436 AC: 2967 AN: 68016

Other (OTH) AF: 0.0397 AC: 84 AN: 2116

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

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.14
Mutation Taster		=168/32	polymorphism

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: rs142025971; hg19: chr15-78558584; COSMIC: COSV106103972; COSMIC: COSV106103972;