3-46979345-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.669

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC12	NM_144716.6	c.-72-2502T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC12	ENST00000292314.6	c.-72-2502T>A		intron_variant		5
CCDC12	ENST00000425441.5	c.-214-2305T>A		intron_variant		5		P1
CCDC12	ENST00000446836.5	c.-111-2502T>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143862 AN: 152138 Hom.: 68580 Cov.: 34

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.: 62 AF XY: 0.988 AC XY: 81 AN XY: 82

Gnomad4 AFR exome AF: 0.900

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.946 AC: 143966 AN: 152256 Hom.: 68624 Cov.: 34 AF XY: 0.948 AC XY: 70550 AN XY: 74438

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.981

Gnomad4 ASJ AF: 0.995

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.955

Alfa AF: 0.969 Hom.: 8913

Bravo AF: 0.938

Asia WGS AF: 0.992 AC: 3450 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.3
Dann	Benign	0.41

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

LitVar

Other links and lift over

dbSNP: rs13062185; hg19: chr3-47020835;