rs138178722

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021254.4(CFAP298):c.77A>C(p.Glu26Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,597,998 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 17 hom. )

Consequence

CFAP298
NM_021254.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.42

Publications

4 publications found

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:54636): (CFAP298-TCP10L readthrough) This locus represents naturally occurring readthrough transcription between the neighboring chromosome 21 open reading frame 59 (C21orf59) and TCP10L (t-complex 10 like) genes on chromosome 21. Readthrough transcripts may encode a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

CFAP298-TCP10L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008645952).

BP6

Variant 21-32612167-T-G is Benign according to our data. Variant chr21-32612167-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00233 (355/152264) while in subpopulation AMR AF = 0.00908 (139/15304). AF 95% confidence interval is 0.00785. There are 2 homozygotes in GnomAd4. There are 176 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP298	NM_021254.4 link	c.77A>C	p.Glu26Ala	missense_variant	Exon 1 of 7	ENST00000290155.8	NP_067077.1	P57076

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP298	ENST00000290155.8 link	c.77A>C	p.Glu26Ala	missense_variant	Exon 1 of 7	1	NM_021254.4	ENSP00000290155.3		P57076
CFAP298-TCP10L	ENST00000673807.1 link	c.77A>C	p.Glu26Ala	missense_variant	Exon 1 of 8			ENSP00000501088.1		A0A669KAY3

Frequencies

GnomAD3 genomes

AF:

0.00233

AC:

355

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00909

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00175

Gnomad OTH

AF:

0.0125

GnomAD2 exomes

AF:

0.00252

AC:

551

AN:

218886

AF XY:

0.00259

show subpopulations

Gnomad AFR exome

AF:

0.000459

Gnomad AMR exome

AF:

0.00625

Gnomad ASJ exome

AF:

0.00760

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00191

Gnomad OTH exome

AF:

0.00601

GnomAD4 exome

AF:

0.00181

AC:

2618

AN:

1445734

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

1376

AN XY:

717476

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33244

American (AMR)

AF:

0.00649

AC:

277

AN:

42706

Ashkenazi Jewish (ASJ)

AF:

0.00728

AC:

187

AN:

25690

East Asian (EAS)

AF:

0.00

AC:

AN:

39008

South Asian (SAS)

AF:

0.00233

AC:

194

AN:

83238

European-Finnish (FIN)

AF:

0.000507

AC:

AN:

51292

Middle Eastern (MID)

AF:

0.0219

AC:

126

AN:

5746

European-Non Finnish (NFE)

AF:

0.00139

AC:

1540

AN:

1104992

Other (OTH)

AF:

0.00384

AC:

230

AN:

59818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

127

254

380

507

634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00233

AC:

355

AN:

152264

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

176

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.000457

AC:

AN:

41554

American (AMR)

AF:

0.00908

AC:

139

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00249

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00176

AC:

120

AN:

68012

Other (OTH)

AF:

0.0123

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00230

Hom.:

Bravo

AF:

0.00277

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00212

AC:

257

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CFAP298: BP4, BS2; CFAP298-TCP10L: BP4, BS2 -

Oct 02, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.079

.;T;.;T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.69

T;T;T;T;T

MetaRNN

Benign

0.0086

T;T;T;T;T

MetaSVM

Benign

-0.95

PhyloP100

2.4

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Benign

0.074

Sift

Benign

0.25

T;T;T;T;T

Sift4G

Benign

0.39

T;T;T;T;.

Polyphen

0.0040, 0.011, 0.0020

.;B;B;B;.

Vest4

0.20, 0.15, 0.12

MVP

0.14

MPC

0.15

ClinPred

0.030

GERP RS

3.7

PromoterAI

-0.087

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.35

gMVP

0.38

Mutation Taster

=49/51

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over