Genetic Variant ENST00000409284.1:c.*4362G>A (chr2-178873542-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000409284.1(CCDC141):c.*4362G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,032 control chromosomes in the GnomAD database, including 2,856 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2856 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

CCDC141
ENST00000409284.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.284

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hypogonadotropic hypogonadism
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CCDC141 links:

ENSG00000287149 (HGNC:):

ENSG00000287149 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409284.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC141	NM_173648.4	MANE Select	c.1900-1230G>A		intron	N/A	NP_775919.3
	CCDC141	NM_001316745.2		c.*4362G>A		3_prime_UTR	Exon 12 of 12	NP_001303674.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CCDC141	ENST00000409284.1	TSL:1	c.*4362G>A	3_prime_UTR	Exon 12 of 12	ENSP00000386503.1
CCDC141	ENST00000443758.7	TSL:5 MANE Select	c.1900-1230G>A	intron	N/A	ENSP00000390190.2
CCDC141	ENST00000343876.6	TSL:1	c.232-1230G>A	intron	N/A	ENSP00000344627.2

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27542

AN:

151914

Hom.:

2854

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.0102

Gnomad SAS

AF:

0.0760

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.209

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.181

AC:

27562

AN:

152032

Hom.:

2856

Cov.:

AF XY:

0.178

AC XY:

13239

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.262

AC:

10868

AN:

41442

American (AMR)

AF:

0.162

AC:

2476

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

818

AN:

3468

East Asian (EAS)

AF:

0.0102

AC:

AN:

5180

South Asian (SAS)

AF:

0.0752

AC:

363

AN:

4824

European-Finnish (FIN)

AF:

0.154

AC:

1621

AN:

10536

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10780

AN:

67996

Other (OTH)

AF:

0.207

AC:

437

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1111

2222

3332

4443

5554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.164

Hom.:

8390

Bravo

AF:

0.186

Asia WGS

AF:

0.0610

AC:

214

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.59

(source)

DANN

Benign

0.51

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over