chr2-178834657-A-G

Position:

• chr2-178834657-A-G

Variant summary

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

The NM_173648.4(CCDC141):​c.4326-217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,784 control chromosomes in the GnomAD database, including 2,750 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2750 hom., cov: 31)
• Consequence: CCDC141 NM_173648.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.158

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 2-178834657-A-G is Benign according to our data. Variant chr2-178834657-A-G is described in ClinVar as [Benign]. Clinvar id is 1277788.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC141	NM_173648.4	c.4326-217T>C		intron_variant		ENST00000443758.7	NP_775919.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC141	ENST00000443758.7	c.4326-217T>C		intron_variant		5	NM_173648.4	ENSP00000390190.2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27398 AN: 151666 Hom.: 2748 Cov.: 31

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.0559

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.217

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.181 AC: 27406 AN: 151784 Hom.: 2750 Cov.: 31 AF XY: 0.175 AC XY: 12984 AN XY: 74174

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.0553

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.214

Alfa AF: 0.201 Hom.: 692

Bravo AF: 0.181

Asia WGS AF: 0.0370 AC: 132 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 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.0
DANN	Benign	0.67

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: rs62175451; hg19: chr2-179699384;