Genetic Variant ENST00000539757.1:n.2325T>C (chr12-9311210-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000539757.1(DDX12B):n.2325T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 1,389,540 control chromosomes in the GnomAD database, including 617,689 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 0.91 ( 62918 hom., cov: 26)

Exomes 𝑓: 0.94 ( 554771 hom. )

Consequence

DDX12B
ENST00000539757.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.58

Publications

8 publications found

Variant links:

COSMIC-nc: COSV62037025

Genes affected

DDX12B (HGNC:38668): (DEAD/H-box helicase 12B%2C pseudogene [Source:HGNC Symbol%3BAcc:HGNC:38668])

DDX12B links:

LOC642846 (HGNC:):

LOC642846 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=-0.63).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000539757.1. 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
	LOC642846	NR_024374.1		n.2435T>C		non_coding_transcript_exon	Exon 21 of 22

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
DDX12B	ENST00000539757.1	TSL:6	n.2325T>C	non_coding_transcript_exon	Exon 22 of 29
ENSG00000299001	ENST00000759736.1		n.139+1831A>G	intron	N/A
ENSG00000299001	ENST00000759737.1		n.108+1831A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.911

AC:

137337

AN:

150750

Hom.:

62874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.835

Gnomad AMI

AF:

0.991

Gnomad AMR

AF:

0.937

Gnomad ASJ

AF:

0.971

Gnomad EAS

AF:

0.713

Gnomad SAS

AF:

0.957

Gnomad FIN

AF:

0.950

Gnomad MID

AF:

0.934

Gnomad NFE

AF:

0.953

Gnomad OTH

AF:

0.896

GnomAD4 exome

AF:

0.944

AC:

1169282

AN:

1238674

Hom.:

554771

Cov.:

AF XY:

0.946

AC XY:

592119

AN XY:

626238

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.829

AC:

24072

AN:

29028

American (AMR)

AF:

0.953

AC:

41791

AN:

43846

Ashkenazi Jewish (ASJ)

AF:

0.964

AC:

23613

AN:

24506

East Asian (EAS)

AF:

0.744

AC:

28353

AN:

38094

South Asian (SAS)

AF:

0.962

AC:

78648

AN:

81784

European-Finnish (FIN)

AF:

0.950

AC:

50212

AN:

52834

Middle Eastern (MID)

AF:

0.944

AC:

4938

AN:

5232

European-Non Finnish (NFE)

AF:

0.954

AC:

868436

AN:

910644

Other (OTH)

AF:

0.934

AC:

49219

AN:

52706

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.369

Heterozygous variant carriers

2488

4976

7464

9952

12440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16218

32436

48654

64872

81090

<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:

0.911

AC:

137432

AN:

150866

Hom.:

62918

Cov.:

AF XY:

0.910

AC XY:

67067

AN XY:

73666

show subpopulations

African (AFR)

AF:

0.835

AC:

34171

AN:

40946

American (AMR)

AF:

0.937

AC:

14261

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.971

AC:

3365

AN:

3464

East Asian (EAS)

AF:

0.712

AC:

3583

AN:

5030

South Asian (SAS)

AF:

0.957

AC:

4534

AN:

4738

European-Finnish (FIN)

AF:

0.950

AC:

9997

AN:

10522

Middle Eastern (MID)

AF:

0.939

AC:

276

AN:

294

European-Non Finnish (NFE)

AF:

0.953

AC:

64473

AN:

67658

Other (OTH)

AF:

0.895

AC:

1870

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

517

1034

1551

2068

2585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.926

Hom.:

16624

Bravo

AF:

0.903

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.55

PhyloP100

3.6

Splicing

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