Variant 15-81134341-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173528.4(CFAP161):c.12C>A(p.Asn4Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,589,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

CFAP161
NM_173528.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.131

Variant links:

Genes affected

CFAP161 (HGNC:26782): (cilia and flagella associated protein 161)

CFAP161 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.00805968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CFAP161	NM_173528.4 linkuse as main transcript	c.12C>A	p.Asn4Lys	missense_variant	1/7	ENST00000286732.5
CFAP161	NM_001353365.2 linkuse as main transcript	c.12C>A	p.Asn4Lys	missense_variant	1/6
CFAP161	XM_006720408.3 linkuse as main transcript	c.-6-929C>A		intron_variant
CFAP161	XM_017021963.2 linkuse as main transcript	c.-6-929C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP161	ENST00000286732.5 linkuse as main transcript	c.12C>A	p.Asn4Lys	missense_variant	1/7	1	NM_173528.4	P1	Q6P656-1
CFAP161	ENST00000560091.5 linkuse as main transcript	c.-6-929C>A		intron_variant		5
CFAP161	ENST00000561216.1 linkuse as main transcript	c.-6-929C>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000911

AC:

AN:

208584

Hom.:

AF XY:

0.000116

AC XY:

AN XY:

111758

show subpopulations

Gnomad AFR exome

AF:

0.00127

Gnomad AMR exome

AF:

0.0000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000783

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000557

AC:

AN:

1437060

Hom.:

Cov.:

AF XY:

0.0000576

AC XY:

AN XY:

711906

show subpopulations

Gnomad4 AFR exome

AF:

0.00195

Gnomad4 AMR exome

AF:

0.0000505

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000367

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.08e-7

Gnomad4 OTH exome

AF:

0.000151

GnomAD4 genome

AF:

0.000538

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000118

Hom.:

Bravo

AF:

0.000586

ESP6500AA

AF:

0.000949

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000915

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.12C>A (p.N4K) alteration is located in exon 1 (coding exon 1) of the CFAP161 gene. This alteration results from a C to A substitution at nucleotide position 12, causing the asparagine (N) at amino acid position 4 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.71

Cadd

Benign

8.5

Dann

Benign

0.84

DEOGEN2

Benign

0.014

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.48

M_CAP

Benign

0.0084

MetaRNN

Benign

0.0081

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.39

REVEL

Benign

0.086

Sift

Benign

0.41

Sift4G

Benign

0.66

Polyphen

0.48

Vest4

0.22

MutPred

0.35

Gain of methylation at N4 (P = 0.0034);

MVP

0.16

MPC

0.35

ClinPred

0.0097

GERP RS

-2.2

Varity_R

0.091

gMVP

0.28

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

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