11-102047486-C-T

Variant names:

• chr11-102047486-C-T
• rs184947491
• NM_032930.3:c.16C>T

Variant summary

Our verdict is Benign. The variant received -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. 14/19 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 38

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 6 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032930.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP300	NM_032930.3	MANE Select	c.16C>T	p.Leu6Phe	missense	Exon 1 of 7	NP_116319.2	Q9BRQ4-1
	CFAP300	NM_001441265.1		c.16C>T	p.Leu6Phe	missense	Exon 1 of 6	NP_001428194.1
	CFAP300	NM_001363505.2		c.16C>T	p.Leu6Phe	missense	Exon 1 of 6	NP_001350434.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP300	ENST00000434758.7	TSL:2 MANE Select	c.16C>T	p.Leu6Phe	missense	Exon 1 of 7	ENSP00000414390.2	Q9BRQ4-1
	CFAP300	ENST00000534360.1	TSL:1	c.16C>T	p.Leu6Phe	missense	Exon 1 of 4	ENSP00000435482.1	Q9BRQ4-3
	CFAP300	ENST00000530659.1	TSL:1	n.19C>T		non_coding_transcript_exon	Exon 1 of 6

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

GnomAD2 exomes AF: 0.00164 AC: 225 AN: 136836 AF XY: 0.00172

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 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

African (AFR) AF: 0.000317 AC: 10 AN: 31584

American (AMR) AF: 0.000700 AC: 25 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.000159 AC: 4 AN: 25170

East Asian (EAS) AF: 0.00129 AC: 46 AN: 35726

South Asian (SAS) AF: 0.00206 AC: 163 AN: 79230

European-Finnish (FIN) AF: 0.000797 AC: 27 AN: 33892

Middle Eastern (MID) AF: 0.000879 AC: 5 AN: 5686

European-Non Finnish (NFE) AF: 0.00205 AC: 2207 AN: 1078702

Other (OTH) AF: 0.00199 AC: 115 AN: 57890

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

African (AFR) AF: 0.000529 AC: 22 AN: 41592

American (AMR) AF: 0.00163 AC: 25 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5168

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4832

European-Finnish (FIN) AF: 0.000848 AC: 9 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00200 AC: 136 AN: 68032

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	CFAP300-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.27
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.021
Sift	Benign	0.58	T
Sift4G	Benign	0.55	T
Polyphen		0.59	P
Vest4		0.053
MVP		0.040
MPC		0.044
ClinPred		0.0017	T
GERP RS		1.7
PromoterAI		0.013	Neutral
Varity_R		0.043
gMVP		0.19
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs184947491; hg19: chr11-101918217;