Genetic Variant CCDC154:c.1878-1G>A (chr16-1434535-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001143980.3(CCDC154):c.1878-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00491 in 1,545,066 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 4 hom., cov: 34)

Exomes 𝑓: 0.0050 ( 29 hom. )

Consequence

CCDC154
NM_001143980.3 splice_acceptor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.94

Variant links:

Genes affected

CCDC154 (HGNC:34454): (coiled-coil domain containing 154) Predicted to be involved in bone mineralization involved in bone maturation. Predicted to act upstream of or within bone resorption; odontogenesis of dentin-containing tooth; and tooth eruption. Predicted to be located in early endosome. [provided by Alliance of Genome Resources, Apr 2022]

CCDC154 links:

PERCC1 (HGNC:52293): (proline and glutamate rich with coiled coil 1) Predicted to be involved in digestive tract morphogenesis and enteroendocrine cell differentiation. Implicated in congenital diarrhea. [provided by Alliance of Genome Resources, Apr 2022]

PERCC1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 16-1434535-C-T is Benign according to our data. Variant chr16-1434535-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645898.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC154	NM_001143980.3 link	c.1878-1G>A		splice_acceptor_variant, intron_variant	Intron 16 of 16	ENST00000389176.4	NP_001137452.1	A6NI56
PERCC1	NM_001365310.2 link	c.*1138C>T		downstream_gene_variant		ENST00000640283.2	NP_001352239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC154	ENST00000389176.4 link	c.1878-1G>A		splice_acceptor_variant, intron_variant	Intron 16 of 16	5	NM_001143980.3	ENSP00000373828.4		A6NI56A0A590PWR5
PERCC1	ENST00000640283.2 link	c.*1138C>T		downstream_gene_variant		5	NM_001365310.2	ENSP00000492108.2		A0A1W2PR82

Frequencies

GnomAD3 genomes

AF:

0.00402

AC:

611

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.0262

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00556

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00468

AC:

698

AN:

149228

Hom.:

AF XY:

0.00466

AC XY:

371

AN XY:

79686

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.00404

Gnomad ASJ exome

AF:

0.0224

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00306

Gnomad FIN exome

AF:

0.000589

Gnomad NFE exome

AF:

0.00507

Gnomad OTH exome

AF:

0.00795

GnomAD4 exome

AF:

0.00500

AC:

6970

AN:

1392792

Hom.:

Cov.:

AF XY:

0.00493

AC XY:

3386

AN XY:

686672

show subpopulations

Gnomad4 AFR exome

AF:

0.000857

Gnomad4 AMR exome

AF:

0.00407

Gnomad4 ASJ exome

AF:

0.0239

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00286

Gnomad4 FIN exome

AF:

0.000875

Gnomad4 NFE exome

AF:

0.00513

Gnomad4 OTH exome

AF:

0.00644

GnomAD4 genome

AF:

0.00402

AC:

612

AN:

152274

Hom.:

Cov.:

AF XY:

0.00365

AC XY:

272

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.0262

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00556

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00638

Hom.:

Bravo

AF:

0.00452

ExAC

AF:

0.00439

AC:

125

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CCDC154: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Pathogenic

0.83

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.95

GERP RS

4.9

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.86

SpliceAI score (max)

0.81

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.81

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over