Variant 2-178834218-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_173648.4(CCDC141):c.4548C>T(p.Val1516=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 1,536,036 control chromosomes in the GnomAD database, including 5,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1312 hom., cov: 32)

Exomes 𝑓: 0.072 ( 4261 hom. )

Consequence

CCDC141
NM_173648.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.92

Variant links:

Genes affected

CCDC141 (HGNC:26821): (coiled-coil domain containing 141) Predicted to be involved in axon guidance and cell adhesion. Predicted to act upstream of or within centrosome localization and cerebral cortex radially oriented cell migration. Predicted to be located in centrosome; cytoplasm; and plasma membrane. Predicted to be active in neuron projection. [provided by Alliance of Genome Resources, Apr 2022]

CCDC141 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 2-178834218-G-A is Benign according to our data. Variant chr2-178834218-G-A is described in ClinVar as [Benign]. Clinvar id is 1272099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC141	NM_173648.4 linkuse as main transcript	c.4548C>T	p.Val1516=	synonymous_variant	24/24	ENST00000443758.7	NP_775919.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC141	ENST00000443758.7 linkuse as main transcript	c.4548C>T	p.Val1516=	synonymous_variant	24/24	5	NM_173648.4	ENSP00000390190	P1	Q6ZP82-2
	ENST00000652826.1 linkuse as main transcript	n.306+5564G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17032

AN:

152014

Hom.:

1309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.0684

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.0783

Gnomad FIN

AF:

0.0630

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0642

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.0835

AC:

11539

AN:

138242

Hom.:

596

AF XY:

0.0824

AC XY:

6158

AN XY:

74776

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.0544

Gnomad ASJ exome

AF:

0.128

Gnomad EAS exome

AF:

0.132

Gnomad SAS exome

AF:

0.0799

Gnomad FIN exome

AF:

0.0704

Gnomad NFE exome

AF:

0.0668

Gnomad OTH exome

AF:

0.0837

GnomAD4 exome

AF:

0.0718

AC:

99340

AN:

1383904

Hom.:

4261

Cov.:

AF XY:

0.0718

AC XY:

49057

AN XY:

682892

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.0589

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.140

Gnomad4 SAS exome

AF:

0.0789

Gnomad4 FIN exome

AF:

0.0727

Gnomad4 NFE exome

AF:

0.0625

Gnomad4 OTH exome

AF:

0.0859

GnomAD4 genome

AF:

0.112

AC:

17062

AN:

152132

Hom.:

1312

Cov.:

AF XY:

0.111

AC XY:

8245

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.0683

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.136

Gnomad4 SAS

AF:

0.0782

Gnomad4 FIN

AF:

0.0630

Gnomad4 NFE

AF:

0.0642

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0782

Hom.:

631

Bravo

AF:

0.119

Asia WGS

AF:

0.111

AC:

384

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

8.8

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

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