rs78585114

Variant names:

• chr2-178834117-G-A
• rs78585114
• NM_173648.4:c.*56C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-178834117-G-A
• chr2-178834117-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173648.4(CCDC141):​c.*56C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 1,504,050 control chromosomes in the GnomAD database, including 6,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (668 hom., cov: 32)
  • Exomes 𝑓: 0.089 (6239 hom.)
• Consequence: CCDC141 NM_173648.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.506
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-178834117-G-A is Benign according to our data. Variant chr2-178834117-G-A is described in ClinVar as Benign. ClinVar VariationId is 1245548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173648.4. 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.*56C>T		3_prime_UTR	Exon 24 of 24	NP_775919.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC141	ENST00000443758.7	TSL:5 MANE Select	c.*56C>T		3_prime_UTR	Exon 24 of 24	ENSP00000390190.2	Q6ZP82-2
	CCDC141	ENST00000922698.1		c.*56C>T		3_prime_UTR	Exon 25 of 25	ENSP00000592757.1
	CCDC141	ENST00000894515.1		c.*56C>T		3_prime_UTR	Exon 23 of 23	ENSP00000564574.1

Frequencies

GnomAD3 genomes AF: 0.0838 AC: 12745 AN: 152088 Hom.: 662 Cov.: 32

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.0636

Gnomad SAS AF: 0.0717

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.0705

GnomAD4 exome AF: 0.0893 AC: 120775 AN: 1351844 Hom.: 6239 Cov.: 27 AF XY: 0.0885 AC XY: 58857 AN XY: 664706

African (AFR) AF: 0.0521 AC: 1603 AN: 30776

American (AMR) AF: 0.243 AC: 8556 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.0615 AC: 1512 AN: 24590

East Asian (EAS) AF: 0.0531 AC: 1875 AN: 35298

South Asian (SAS) AF: 0.0743 AC: 5747 AN: 77300

European-Finnish (FIN) AF: 0.0799 AC: 2677 AN: 33510

Middle Eastern (MID) AF: 0.0554 AC: 261 AN: 4708

European-Non Finnish (NFE) AF: 0.0889 AC: 93742 AN: 1054006

Other (OTH) AF: 0.0851 AC: 4802 AN: 56460

GnomAD4 genome AF: 0.0840 AC: 12782 AN: 152206 Hom.: 668 Cov.: 32 AF XY: 0.0836 AC XY: 6219 AN XY: 74398

African (AFR) AF: 0.0549 AC: 2280 AN: 41558

American (AMR) AF: 0.165 AC: 2525 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 189 AN: 3466

East Asian (EAS) AF: 0.0638 AC: 330 AN: 5176

South Asian (SAS) AF: 0.0719 AC: 346 AN: 4810

European-Finnish (FIN) AF: 0.0746 AC: 791 AN: 10602

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0897 AC: 6098 AN: 68006

Other (OTH) AF: 0.0697 AC: 147 AN: 2108

Alfa AF: 0.0863 Hom.: 402

Bravo AF: 0.0933

Asia WGS AF: 0.0610 AC: 210 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.40
PhyloP100		0.51
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: rs78585114; hg19: chr2-179698844; COSMIC: COSV55368950; COSMIC: COSV55368950;