Variant 21-32602236-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000382549.8(CFAP298):c.*853C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000446 in 1,591,272 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 2 hom. )

Consequence

CFAP298
ENST00000382549.8 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.11

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 21-32602236-G-C is Benign according to our data. Variant chr21-32602236-G-C is described in ClinVar as [Benign]. Clinvar id is 3039765.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00219 (334/152298) while in subpopulation AFR AF= 0.00772 (321/41570). AF 95% confidence interval is 0.00703. There are 4 homozygotes in gnomad4. There are 168 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP298	NM_021254.4 linkuse as main transcript	c.762+36C>G		intron_variant		ENST00000290155.8
CFAP298-TCP10L	NR_146638.2 linkuse as main transcript	n.800+925C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP298	ENST00000290155.8 linkuse as main transcript	c.762+36C>G		intron_variant		1	NM_021254.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00215

AC:

327

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00755

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000670

AC:

168

AN:

250666

Hom.:

AF XY:

0.000494

AC XY:

AN XY:

135508

show subpopulations

Gnomad AFR exome

AF:

0.00867

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000261

AC:

376

AN:

1438974

Hom.:

Cov.:

AF XY:

0.000245

AC XY:

176

AN XY:

717112

show subpopulations

Gnomad4 AFR exome

AF:

0.00781

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000513

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000275

Gnomad4 OTH exome

AF:

0.000855

GnomAD4 genome

AF:

0.00219

AC:

334

AN:

152298

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

168

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00772

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000857

Hom.:

Bravo

AF:

0.00247

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CFAP298-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.10

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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