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. Variant has been reported in ClinVar as (no stars).

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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005528.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAJC4	NM_005528.4	MANE Select	c.180+93C>T	intron	N/A	NP_005519.2	Q9NNZ3
DNAJC4	NM_001307980.1		c.180+93C>T	intron	N/A	NP_001294909.1	Q6PIN0
DNAJC4	NM_001307981.1		c.180+93C>T	intron	N/A	NP_001294910.1	Q86VG4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAJC4	ENST00000628077.3	TSL:5 MANE Select	c.180+93C>T	intron	N/A	ENSP00000486499.2	Q9NNZ3
DNAJC4	ENST00000321460.5	TSL:1	c.180+93C>T	intron	N/A	ENSP00000320548.5	J3KNJ8
DNAJC4	ENST00000321685.7	TSL:1	c.180+93C>T	intron	N/A	ENSP00000396896.2	Q9NNZ3

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over