2-178873542-C-T

Variant names:

• chr2-178873542-C-T
• rs11693319
• ENST00000409284.1:c.*4362G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 7 publications found

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

ENSG00000287149 (HGNC:):

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC141	NM_173648.4	c.1900-1230G>A		intron_variant	Intron 12 of 23	ENST00000443758.7	NP_775919.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC141	ENST00000443758.7	c.1900-1230G>A		intron_variant	Intron 12 of 23	5	NM_173648.4	ENSP00000390190.2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27542 AN: 151914 Hom.: 2854 Cov.: 32

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: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.181 AC: 27562 AN: 152032 Hom.: 2856 Cov.: 32 AF XY: 0.178 AC XY: 13239 AN XY: 74308

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: 53 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: 67 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10780 AN: 67996

Other (OTH) AF: 0.207 AC: 437 AN: 2114

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.51
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11693319; hg19: chr2-179738269;