chr1-43156206-A-G

Position:

chr1-43156206-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001101376.3(CFAP144):c.298A>G(p.Ile100Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000925 in 1,613,608 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 1 hom. )

Consequence

CFAP144
NM_001101376.3 missense, splice_region

Scores

Splicing: ADA: 0.000007317

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.134

Variant links:

Genes affected

CFAP144 (HGNC:34347): (cilia and flagella associated protein 144) Predicted to be located in centrosome and ciliary basal body. Predicted to be active in ciliary base. [provided by Alliance of Genome Resources, Apr 2022]

CFAP144 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012067109).

BP6

Variant 1-43156206-A-G is Benign according to our data. Variant chr1-43156206-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1710363.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CFAP144	NM_001101376.3 linkuse as main transcript	c.298A>G	p.Ile100Val	missense_variant, splice_region_variant	4/4	ENST00000335282.5
CFAP144	XM_005270875.6 linkuse as main transcript	c.346A>G	p.Ile116Val	missense_variant, splice_region_variant	4/4
CFAP144	XM_005270876.5 linkuse as main transcript	c.262A>G	p.Ile88Val	missense_variant, splice_region_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP144	ENST00000335282.5 linkuse as main transcript	c.298A>G	p.Ile100Val	missense_variant, splice_region_variant	4/4	2	NM_001101376.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000532

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000897

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000481

AC:

120

AN:

249254

Hom.:

AF XY:

0.000555

AC XY:

AN XY:

135216

show subpopulations

Gnomad AFR exome

AF:

0.000452

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000982

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000966

AC:

1412

AN:

1461484

Hom.:

Cov.:

AF XY:

0.000956

AC XY:

695

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00124

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000532

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.000459

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000715

Hom.:

Bravo

AF:

0.000468

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000753

AC:

ESP6500EA

AF:

0.00108

AC:

ExAC

AF:

0.000447

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.00113

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Aug 18, 2022

Gene of Uncertain Significance -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 03, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.6

DANN

Benign

0.30

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.46

T;T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0090

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.070

N;N;N

REVEL

Benign

0.016

Sift

Benign

0.66

T;T;T

Sift4G

Benign

0.92

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.10

MVP

0.030

MPC

0.057

ClinPred

0.0095

GERP RS

0.11

Varity_R

0.022

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000073

dbscSNV1_RF

Benign

0.0

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