Genetic Variant DNAJC4:c.180+93C>T (chr11-64232057-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005528.4(DNAJC4):c.180+93C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,332,322 control chromosomes in the GnomAD database, including 127,371 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 0.39 ( 12288 hom., cov: 31)

Exomes 𝑓: 0.44 ( 115083 hom. )

Consequence

DNAJC4
NM_005528.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.24

Publications

22 publications found

Variant links:

Genes affected

DNAJC4 (HGNC:5271): (DnaJ heat shock protein family (Hsp40) member C4) Predicted to be involved in response to unfolded protein. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC4 links:

ENSG00000256116 (HGNC:):

ENSG00000256116 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DNAJC4	NM_005528.4 link	c.180+93C>T	intron_variant	Intron 2 of 5	ENST00000628077.3	NP_005519.2	Q9NNZ3
DNAJC4	NM_001307980.1 link	c.180+93C>T	intron_variant	Intron 2 of 4		NP_001294909.1	Q9NNZ3J3KNJ8Q6PIN0
DNAJC4	NM_001307981.1 link	c.180+93C>T	intron_variant	Intron 2 of 4		NP_001294910.1	Q9NNZ3Q86VG4
DNAJC4	XM_047426865.1 link	c.180+93C>T	intron_variant	Intron 2 of 5		XP_047282821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC4	ENST00000628077.3 link	c.180+93C>T		intron_variant	Intron 2 of 5	5	NM_005528.4	ENSP00000486499.2		Q9NNZ3Q96FY5

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58946

AN:

151738

Hom.:

12285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.397

Gnomad EAS

AF:

0.622

Gnomad SAS

AF:

0.468

Gnomad FIN

AF:

0.425

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.426

GnomAD4 exome

AF:

0.438

AC:

517627

AN:

1180466

Hom.:

115083

Cov.:

AF XY:

0.441

AC XY:

263431

AN XY:

597334

show subpopulations

African (AFR)

AF:

0.228

AC:

6377

AN:

27946

American (AMR)

AF:

0.480

AC:

19233

AN:

40100

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

9538

AN:

23774

East Asian (EAS)

AF:

0.588

AC:

22305

AN:

37950

South Asian (SAS)

AF:

0.473

AC:

37229

AN:

78730

European-Finnish (FIN)

AF:

0.415

AC:

18499

AN:

44610

Middle Eastern (MID)

AF:

0.484

AC:

2542

AN:

5248

European-Non Finnish (NFE)

AF:

0.436

AC:

379472

AN:

870770

Other (OTH)

AF:

0.437

AC:

22432

AN:

51338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

14489

28978

43468

57957

72446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10432

20864

31296

41728

52160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.388

AC:

58970

AN:

151856

Hom.:

12288

Cov.:

AF XY:

0.392

AC XY:

29055

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.235

AC:

9733

AN:

41380

American (AMR)

AF:

0.439

AC:

6697

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

1379

AN:

3470

East Asian (EAS)

AF:

0.623

AC:

3212

AN:

5158

South Asian (SAS)

AF:

0.468

AC:

2249

AN:

4810

European-Finnish (FIN)

AF:

0.425

AC:

4489

AN:

10550

Middle Eastern (MID)

AF:

0.479

AC:

140

AN:

292

European-Non Finnish (NFE)

AF:

0.439

AC:

29814

AN:

67916

Other (OTH)

AF:

0.424

AC:

894

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1744

3488

5231

6975

8719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.427

Hom.:

24139

Bravo

AF:

0.386

Asia WGS

AF:

0.485

AC:

1687

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.8

(source)

DANN

Benign

0.57

PhyloP100

-1.2

PromoterAI

0.028

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over