rs3795283

Variant names:

• chr1-1985148-G-A
• rs3795283
• NM_001304360.2:c.500+238C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-1985148-G-A
• chr1-1985148-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001304360.2(CFAP74):​c.500+238C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000318 in 314,860 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: CFAP74 NM_001304360.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP74	NM_001304360.2	c.500+238C>T		intron_variant	Intron 6 of 38	ENST00000682832.2	NP_001291289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP74	ENST00000682832.2	c.500+238C>T		intron_variant	Intron 6 of 38		NM_001304360.2	ENSP00000508276.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000318 AC: 1 AN: 314860 Hom.: 0 Cov.: 2 AF XY: 0.00000614 AC XY: 1 AN XY: 162788

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 10506

American (AMR) AF: 0.00 AC: 0 AN: 15670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10552

East Asian (EAS) AF: 0.00 AC: 0 AN: 26360

South Asian (SAS) AF: 0.00 AC: 0 AN: 21496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1424

European-Non Finnish (NFE) AF: 0.00000530 AC: 1 AN: 188722

Other (OTH) AF: 0.00 AC: 0 AN: 18880

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.8
DANN	Benign	0.71
PhyloP100		0.080

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3795283; hg19: chr1-1916587;