ENST00000605875.1:c.-108T>C

Variant names:

• chr3-46979533-A-G
• rs13062516
• ENST00000605875.1:c.-108T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000605875.1(CCDC12):​c.-108T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.952 in 194,522 control chromosomes in the GnomAD database, including 88,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (68146 hom., cov: 34)
  • Exomes 𝑓: 0.99 (20751 hom.)
• Consequence: CCDC12 ENST00000605875.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.397

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-46979533-A-G is Benign according to our data. Variant chr3-46979533-A-G is described in ClinVar as [Benign]. Clinvar id is 1251507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
CCDC12	NM_144716.6	c.-73+2399T>C		intron_variant	Intron 1 of 7		NP_653317.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC12	ENST00000605875.1	c.-108T>C		5_prime_UTR_variant	Exon 1 of 4	5		ENSP00000473887.2
CCDC12	ENST00000292314.6	c.-73+2399T>C		intron_variant	Intron 1 of 7	5		ENSP00000292314.2
CCDC12	ENST00000425441.5	c.-215+2399T>C		intron_variant	Intron 1 of 8	5		ENSP00000416263.2

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143290 AN: 152134 Hom.: 68102 Cov.: 34

Gnomad AFR AF: 0.799

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.980

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: 0.952

GnomAD4 exome AF: 0.990 AC: 41858 AN: 42270 Hom.: 20751 Cov.: 0 AF XY: 0.991 AC XY: 21359 AN XY: 21548

Gnomad4 AFR exome AF: 0.808

Gnomad4 AMR exome AF: 0.980

Gnomad4 ASJ exome AF: 0.995

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.979

GnomAD4 genome AF: 0.942 AC: 143394 AN: 152252 Hom.: 68146 Cov.: 34 AF XY: 0.944 AC XY: 70286 AN XY: 74448

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.980

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: 0.953

Alfa AF: 0.974 Hom.: 3981

Bravo AF: 0.937

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.58

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: rs13062516; hg19: chr3-47021023;