rs61735781

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021254.4(CFAP298):c.622G>A(p.Val208Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0059 in 1,614,212 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V208V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 53 hom. )

Consequence

CFAP298
NM_021254.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.57

Variant links:

Genes affected

CFAP298 (HGNC:1301): (cilia and flagella associated protein 298) This gene encodes a protein that plays a critical role in dynein arm assembly and motile cilia function. Mutations in this gene result in primary ciliary dyskinesia. Naturally occuring readthrough transcription occurs from this locus to the downstream t-complex 10 like (TCP10L) gene. [provided by RefSeq, Apr 2017]

CFAP298 links:

CFAP298-TCP10L (HGNC:):

CFAP298-TCP10L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00909254).

BP6

Variant 21-32603205-C-T is Benign according to our data. Variant chr21-32603205-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32603205-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00436 (664/152362) while in subpopulation NFE AF= 0.00678 (461/68040). AF 95% confidence interval is 0.00626. There are 2 homozygotes in gnomad4. There are 322 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP298	NM_021254.4 linkuse as main transcript	c.622G>A	p.Val208Met	missense_variant	5/7	ENST00000290155.8
CFAP298-TCP10L	NR_146638.2 linkuse as main transcript	n.756G>A		non_coding_transcript_exon_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP298	ENST00000290155.8 linkuse as main transcript	c.622G>A	p.Val208Met	missense_variant	5/7	1	NM_021254.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00436

AC:

664

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00989

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00461

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00677

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00422

AC:

1062

AN:

251480

Hom.:

AF XY:

0.00444

AC XY:

603

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00225

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00640

Gnomad FIN exome

AF:

0.00430

Gnomad NFE exome

AF:

0.00563

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00607

AC:

8867

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00605

AC XY:

4402

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00659

Gnomad4 FIN exome

AF:

0.00453

Gnomad4 NFE exome

AF:

0.00673

Gnomad4 OTH exome

AF:

0.00642

GnomAD4 genome

AF:

0.00436

AC:

664

AN:

152362

Hom.:

Cov.:

AF XY:

0.00432

AC XY:

322

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.00461

Gnomad4 NFE

AF:

0.00678

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00536

Hom.:

Bravo

AF:

0.00393

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.00446

AC:

542

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00616

EpiControl

AF:

0.00581

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 01, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 26, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;T;.;T

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.0091

T;T;T;T

MetaSVM

Uncertain

0.014

MutationTaster

Benign

1.0

D;D;D;D

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

0.99, 0.99

.;D;D;D

Vest4

0.55, 0.34, 0.60

MVP

0.16

MPC

0.51

ClinPred

0.013

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.96

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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