dbSNP rs13062185: CCDC12:c.-72-2502T>A (chr3-46979345-A-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_144716.6(CCDC12):c.-72-2502T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 152,382 control chromosomes in the GnomAD database, including 68,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.95 ( 68624 hom., cov: 34)

Exomes 𝑓: 0.99 ( 62 hom. )

Consequence

CCDC12
NM_144716.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.669

Publications

2 publications found

Variant links:

Genes affected

CCDC12 (HGNC:28332): (coiled-coil domain containing 12) Predicted to be part of U2-type spliceosomal complex and post-mRNA release spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

CCDC12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-46979345-A-T is Benign according to our data. Variant chr3-46979345-A-T is described in ClinVar as Benign. ClinVar VariationId is 1288588.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144716.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC12	NM_144716.6		c.-72-2502T>A		intron	N/A	NP_653317.2	J3KR35

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC12	ENST00000292314.6	TSL:5	c.-72-2502T>A	intron	N/A	ENSP00000292314.2	J3KR35
CCDC12	ENST00000425441.5	TSL:5	c.-214-2305T>A	intron	N/A	ENSP00000416263.2	Q8WUD4
CCDC12	ENST00000446836.5	TSL:3	c.-111-2502T>A	intron	N/A	ENSP00000387490.2	C9JUN5

Frequencies

GnomAD3 genomes

AF:

0.946

AC:

143862

AN:

152138

Hom.:

68580

Cov.:

show subpopulations

Gnomad AFR

AF:

0.812

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.981

Gnomad ASJ

AF:

0.995

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.955

GnomAD4 exome

AF:

0.992

AC:

125

AN:

126

Hom.:

AF XY:

0.988

AC XY:

AN XY:

show subpopulations

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

African (AFR)

AF:

0.900

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

⚠️ 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: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.946

AC:

143966

AN:

152256

Hom.:

68624

Cov.:

AF XY:

0.948

AC XY:

70550

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.812

AC:

33713

AN:

41526

American (AMR)

AF:

0.981

AC:

15016

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.995

AC:

3456

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5154

AN:

5154

South Asian (SAS)

AF:

1.00

AC:

4826

AN:

4828

European-Finnish (FIN)

AF:

1.00

AC:

10626

AN:

10626

Middle Eastern (MID)

AF:

0.986

AC:

290

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67952

AN:

68026

Other (OTH)

AF:

0.955

AC:

2021

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

349

698

1047

1396

1745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<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:

0.969

Hom.:

8913

Bravo

AF:

0.938

Asia WGS

AF:

0.992

AC:

3450

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.3

(source)

DANN

Benign

0.41

PhyloP100

-0.67

PromoterAI

0.011

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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