rs3838975

Variant names:

• chr1-1955672-GC-G
• rs3838975
• NM_001304360.2:c.2176+18delG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001304360.2(CFAP74):​c.2176+18delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,612,216 control chromosomes in the GnomAD database, including 54,719 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4067 hom., cov: 28)
  • Exomes 𝑓: 0.26 (50652 hom.)
• Consequence: CFAP74 NM_001304360.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 7 publications found

Genes affected

CFAP74 (HGNC:29368): (cilia and flagella associated protein 74) Predicted to be involved in axoneme assembly. Predicted to be located in axoneme. [provided by Alliance of Genome Resources, Apr 2022]

CFAP74 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 49, without situs inversus

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP74	NM_001304360.2	c.2176+18delG		intron_variant	Intron 18 of 38	ENST00000682832.2	NP_001291289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP74	ENST00000682832.2	c.2176+18delG		intron_variant	Intron 18 of 38		NM_001304360.2	ENSP00000508276.2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33381 AN: 151792 Hom.: 4068 Cov.: 28

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.222

GnomAD2 exomes AF: 0.184 AC: 39879 AN: 216886 AF XY: 0.187

Gnomad AFR exome AF: 0.0848

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.128

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.260 AC: 379999 AN: 1460304 Hom.: 50652 Cov.: 29 AF XY: 0.259 AC XY: 188265 AN XY: 726472

African (AFR) AF: 0.137 AC: 4581 AN: 33450

American (AMR) AF: 0.236 AC: 10553 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 6703 AN: 26084

East Asian (EAS) AF: 0.260 AC: 10292 AN: 39598

South Asian (SAS) AF: 0.190 AC: 16379 AN: 86236

European-Finnish (FIN) AF: 0.225 AC: 11933 AN: 53130

Middle Eastern (MID) AF: 0.254 AC: 1460 AN: 5754

European-Non Finnish (NFE) AF: 0.273 AC: 303138 AN: 1111082

Other (OTH) AF: 0.248 AC: 14960 AN: 60290

GnomAD4 genome AF: 0.220 AC: 33376 AN: 151912 Hom.: 4067 Cov.: 28 AF XY: 0.216 AC XY: 16024 AN XY: 74236

African (AFR) AF: 0.140 AC: 5813 AN: 41462

American (AMR) AF: 0.217 AC: 3314 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3466

East Asian (EAS) AF: 0.210 AC: 1074 AN: 5126

South Asian (SAS) AF: 0.182 AC: 877 AN: 4816

European-Finnish (FIN) AF: 0.225 AC: 2372 AN: 10532

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18272 AN: 67912

Other (OTH) AF: 0.219 AC: 463 AN: 2112

Alfa AF: 0.130 Hom.: 438

Asia WGS AF: 0.183 AC: 638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.088

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: rs3838975; hg19: chr1-1887111; COSMIC: COSV54565097; COSMIC: COSV54565097;