11-102047486-C-T

Position:

• chr11-102047486-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032930.3(CFAP300):​c.16C>T​(p.Leu6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,535,916 control chromosomes in the GnomAD database, including 7 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 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (6 hom.)
• Consequence: CFAP300 NM_032930.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.270

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030524433).
• BP6: Variant 11-102047486-C-T is Benign according to our data. Variant chr11-102047486-C-T is described in ClinVar as [Benign]. Clinvar id is 1681444.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00157 (239/152338) while in subpopulation EAS AF= 0.00213 (11/5168). AF 95% confidence interval is 0.00173. There are 1 homozygotes in gnomad4. There are 112 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP300	NM_032930.3	c.16C>T	p.Leu6Phe	missense_variant	1/7	ENST00000434758.7	NP_116319.2
CFAP300	NM_001363505.2	c.16C>T	p.Leu6Phe	missense_variant	1/6		NP_001350434.1
CFAP300	NM_001195005.2	c.16C>T	p.Leu6Phe	missense_variant	1/4		NP_001181934.1
CFAP300	XM_005271713.5	c.16C>T	p.Leu6Phe	missense_variant	1/6		XP_005271770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP300	ENST00000434758.7	c.16C>T	p.Leu6Phe	missense_variant	1/7	2	NM_032930.3	ENSP00000414390	P1
CFAP300	ENST00000534360.1	c.16C>T	p.Leu6Phe	missense_variant	1/4	1		ENSP00000435482
CFAP300	ENST00000530659.1	n.19C>T		non_coding_transcript_exon_variant	1/6	1
CFAP300	ENST00000526781.5	c.16C>T	p.Leu6Phe	missense_variant	1/6	3		ENSP00000433074

Frequencies

GnomAD3 genomes AF: 0.00157 AC: 239 AN: 152220 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00200

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00164 AC: 225 AN: 136836 Hom.: 1 AF XY: 0.00172 AC XY: 128 AN XY: 74320

Gnomad AFR exome AF: 0.000466

Gnomad AMR exome AF: 0.000776

Gnomad ASJ exome AF: 0.000241

Gnomad EAS exome AF: 0.00276

Gnomad SAS exome AF: 0.00204

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00207

Gnomad OTH exome AF: 0.00144

GnomAD4 exome AF: 0.00188 AC: 2602 AN: 1383578 Hom.: 6 Cov.: 31 AF XY: 0.00191 AC XY: 1303 AN XY: 682758

Gnomad4 AFR exome AF: 0.000317

Gnomad4 AMR exome AF: 0.000700

Gnomad4 ASJ exome AF: 0.000159

Gnomad4 EAS exome AF: 0.00129

Gnomad4 SAS exome AF: 0.00206

Gnomad4 FIN exome AF: 0.000797

Gnomad4 NFE exome AF: 0.00205

Gnomad4 OTH exome AF: 0.00199

GnomAD4 genome AF: 0.00157 AC: 239 AN: 152338 Hom.: 1 Cov.: 32 AF XY: 0.00150 AC XY: 112 AN XY: 74498

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.000848

Gnomad4 NFE AF: 0.00200

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00201 Hom.: 0

Bravo AF: 0.00142

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00208 AC: 8

ExAC AF: 0.000712 AC: 13

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

CFAP300-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 03, 2022

This variant is classified as likely 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	0.056
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.6
DANN	Benign	0.80
DEOGEN2	Benign	0.020	T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.41	T;T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.0031	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-0.24	N;N;N
REVEL	Benign	0.021
Sift	Benign	0.58	T;T;T
Sift4G	Benign	0.55	T;T;T
Polyphen		0.59	P;.;.
Vest4		0.053
MVP		0.040
MPC		0.044
ClinPred		0.0017	T
GERP RS		1.7
Varity_R		0.043
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs184947491; hg19: chr11-101918217;