rs6632450

Variant names:

• chrX-35975337-C-T
• rs6632450
• NM_001304548.2:c.2445C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001304548.2(CFAP47):​c.2445C>T​(p.Asp815Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 1,189,464 control chromosomes in the GnomAD database, including 5,531 homozygotes. There are 36,583 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1222 hom., 4929 hem., cov: 23)
  • Exomes 𝑓: 0.086 (4309 hom. 31654 hem.)
• Consequence: CFAP47 NM_001304548.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 10 publications found

Genes affected

CFAP47 (HGNC:26708): (cilia and flagella associated protein 47) While this gene is well-supported by transcript data, no functional information on its protein product is currently available. [provided by RefSeq, Dec 2009]

CFAP47 Gene-Disease associations (from GenCC):

• polycystic kidney disease

  Inheritance: XL Classification: LIMITED, NO_KNOWN Submitted by: University of Washington Center for Rare Disease Research (UW-CRDR), ClinGen
• spermatogenic failure, X-linked, 3

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=0.016 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304548.2. 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
	CFAP47	NM_001304548.2	MANE Select	c.2445C>T	p.Asp815Asp	synonymous	Exon 14 of 64	NP_001291477.1	Q6ZTR5-5
	CFAP47	NM_152632.4		c.2445C>T	p.Asp815Asp	synonymous	Exon 14 of 16	NP_689845.2	Q6ZTR5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP47	ENST00000378653.8	TSL:5 MANE Select	c.2445C>T	p.Asp815Asp	synonymous	Exon 14 of 64	ENSP00000367922.5	Q6ZTR5-5
	CFAP47	ENST00000493930.1	TSL:1	n.*82C>T		non_coding_transcript_exon	Exon 14 of 16	ENSP00000433564.1	Q6ZTR5-2
	CFAP47	ENST00000493930.1	TSL:1	n.*82C>T		3_prime_UTR	Exon 14 of 16	ENSP00000433564.1	Q6ZTR5-2

Frequencies

GnomAD3 genomes AF: 0.149 AC: 16452 AN: 110696 Hom.: 1215 Cov.: 23

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.0438

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.162

GnomAD2 exomes AF: 0.149 AC: 25989 AN: 173981 AF XY: 0.140

Gnomad AFR exome AF: 0.266

Gnomad AMR exome AF: 0.243

Gnomad ASJ exome AF: 0.110

Gnomad EAS exome AF: 0.307

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.0637

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.0863 AC: 93087 AN: 1078717 Hom.: 4309 Cov.: 27 AF XY: 0.0913 AC XY: 31654 AN XY: 346631

African (AFR) AF: 0.265 AC: 6831 AN: 25813

American (AMR) AF: 0.250 AC: 8405 AN: 33575

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 2011 AN: 18903

East Asian (EAS) AF: 0.254 AC: 7600 AN: 29898

South Asian (SAS) AF: 0.241 AC: 12488 AN: 51774

European-Finnish (FIN) AF: 0.112 AC: 4500 AN: 40324

Middle Eastern (MID) AF: 0.140 AC: 570 AN: 4059

European-Non Finnish (NFE) AF: 0.0552 AC: 45734 AN: 829021

Other (OTH) AF: 0.109 AC: 4948 AN: 45350

GnomAD4 genome AF: 0.149 AC: 16500 AN: 110747 Hom.: 1222 Cov.: 23 AF XY: 0.149 AC XY: 4929 AN XY: 33017

African (AFR) AF: 0.254 AC: 7728 AN: 30467

American (AMR) AF: 0.232 AC: 2388 AN: 10287

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 265 AN: 2641

East Asian (EAS) AF: 0.296 AC: 1026 AN: 3463

South Asian (SAS) AF: 0.258 AC: 682 AN: 2642

European-Finnish (FIN) AF: 0.123 AC: 719 AN: 5840

Middle Eastern (MID) AF: 0.126 AC: 27 AN: 214

European-Non Finnish (NFE) AF: 0.0637 AC: 3377 AN: 52995

Other (OTH) AF: 0.171 AC: 258 AN: 1513

Alfa AF: 0.125 Hom.: 1713

Bravo AF: 0.162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.19
PhyloP100		0.016
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs6632450; hg19: chrX-35993454; COSMIC: COSV52882191;