11-102047477-A-G

Position:

chr11-102047477-A-G

Variant summary

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

The NM_032930.3(CFAP300):c.7A>G(p.Thr3Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000525 in 1,535,794 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

CFAP300
NM_032930.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.997

Variant links:

Genes affected

CFAP300 (HGNC:28188): (cilia and flagella associated protein 300) Predicted to be located in cytoplasm and motile cilium. Implicated in primary ciliary dyskinesia 38. [provided by Alliance of Genome Resources, Apr 2022]

CFAP300 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004224479).

BP6

Variant 11-102047477-A-G is Benign according to our data. Variant chr11-102047477-A-G is described in ClinVar as [Benign]. Clinvar id is 1681443.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00257 (391/152326) while in subpopulation AFR AF= 0.00894 (372/41588). AF 95% confidence interval is 0.0082. There are 1 homozygotes in gnomad4. There are 184 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CFAP300	NM_032930.3 linkuse as main transcript	c.7A>G	p.Thr3Ala	missense_variant	1/7	ENST00000434758.7	NP_116319.2
CFAP300	NM_001363505.2 linkuse as main transcript	c.7A>G	p.Thr3Ala	missense_variant	1/6		NP_001350434.1
CFAP300	NM_001195005.2 linkuse as main transcript	c.7A>G	p.Thr3Ala	missense_variant	1/4		NP_001181934.1
CFAP300	XM_005271713.5 linkuse as main transcript	c.7A>G	p.Thr3Ala	missense_variant	1/6		XP_005271770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP300	ENST00000434758.7 linkuse as main transcript	c.7A>G	p.Thr3Ala	missense_variant	1/7	2	NM_032930.3	ENSP00000414390	P1	Q9BRQ4-1
CFAP300	ENST00000534360.1 linkuse as main transcript	c.7A>G	p.Thr3Ala	missense_variant	1/4	1		ENSP00000435482		Q9BRQ4-3
CFAP300	ENST00000530659.1 linkuse as main transcript	n.10A>G		non_coding_transcript_exon_variant	1/6	1
CFAP300	ENST00000526781.5 linkuse as main transcript	c.7A>G	p.Thr3Ala	missense_variant	1/6	3		ENSP00000433074

Frequencies

GnomAD3 genomes

AF:

0.00257

AC:

391

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00897

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000556

AC:

AN:

136810

Hom.:

AF XY:

0.000525

AC XY:

AN XY:

74308

show subpopulations

Gnomad AFR exome

AF:

0.0112

Gnomad AMR exome

AF:

0.000123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000300

AC:

415

AN:

1383468

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

177

AN XY:

682714

show subpopulations

Gnomad4 AFR exome

AF:

0.0118

Gnomad4 AMR exome

AF:

0.000364

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.000449

GnomAD4 genome

AF:

0.00257

AC:

391

AN:

152326

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

184

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00894

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00264

Hom.:

Bravo

AF:

0.00296

ExAC

AF:

0.000330

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

CFAP300-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 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

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.7

DANN

Benign

0.42

DEOGEN2

Benign

0.011

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.34

T;T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0042

T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

0.85

N;N;N

REVEL

Benign

0.042

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.079

MVP

0.030

MPC

0.035

ClinPred

0.0012

GERP RS

0.40

Varity_R

0.036

gMVP

0.28

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