Genetic Variant NM_001304360.2:c.500+238C>T (chr1-1985148-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0800

Publications

0 publications found

Variant links:

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

CFAP74 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.500+238C>T		intron_variant	Intron 6 of 38	ENST00000682832.2	NP_001291289.1	Q9C0B2A0A804HLA9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP74	ENST00000682832.2 link	c.500+238C>T		intron_variant	Intron 6 of 38		NM_001304360.2	ENSP00000508276.2		A0A804HLA9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000318

AC:

AN:

314860

Hom.:

Cov.:

AF XY:

0.00000614

AC XY:

AN XY:

162788

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

10506

American (AMR)

AF:

0.00

AC:

AN:

15670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10552

East Asian (EAS)

AF:

0.00

AC:

AN:

26360

South Asian (SAS)

AF:

0.00

AC:

AN:

21496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1424

European-Non Finnish (NFE)

AF:

0.00000530

AC:

AN:

188722

Other (OTH)

AF:

0.00

AC:

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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over