Genetic Variant CFAP96:p.Val259TrpfsTer29 (chr4-185445023-TG-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001114357.3(CFAP96):c.775delG(p.Val259TrpfsTer29) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,551,602 control chromosomes in the GnomAD database, including 197 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.011 ( 13 hom., cov: 32)

Exomes 𝑓: 0.013 ( 184 hom. )

Consequence

CFAP96
NM_001114357.3 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.320

Variant links:

Genes affected

CFAP96 (HGNC:34346): (cilia and flagella associated protein 96) Located in 9+0 non-motile cilium; centrosome; and cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

CFAP96 links:

CCDC110 (HGNC:28504): (coiled-coil domain containing 110) Predicted to be located in nucleus. Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

CCDC110 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 4-185445023-TG-T is Benign according to our data. Variant chr4-185445023-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 809709.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0133 (18547/1399316) while in subpopulation MID AF= 0.0246 (140/5696). AF 95% confidence interval is 0.0213. There are 184 homozygotes in gnomad4_exome. There are 9231 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP96	NM_001114357.3 link	c.775delG	p.Val259TrpfsTer29	frameshift_variant	Exon 7 of 8	ENST00000378850.5	NP_001107829.1	A7E2U8
CCDC110	NM_152775.4 link	c.*478delC		downstream_gene_variant		ENST00000307588.8	NP_689988.1	Q8TBZ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C4orf47	ENST00000378850.5 link	c.775delG	p.Val259TrpfsTer29	frameshift_variant	Exon 7 of 8	1	NM_001114357.3	ENSP00000368127.4		A7E2U8
CCDC110	ENST00000307588.8 link	c.*478delC		downstream_gene_variant		1	NM_152775.4	ENSP00000306776.3		Q8TBZ0-1

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1673

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00498

Gnomad FIN

AF:

0.0256

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0140

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0135

AC:

2087

AN:

154028

Hom.:

AF XY:

0.0135

AC XY:

1106

AN XY:

81724

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.0285

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00790

Gnomad FIN exome

AF:

0.0275

Gnomad NFE exome

AF:

0.0146

Gnomad OTH exome

AF:

0.0159

GnomAD4 exome

AF:

0.0133

AC:

18547

AN:

1399316

Hom.:

184

Cov.:

AF XY:

0.0134

AC XY:

9231

AN XY:

690164

show subpopulations

Gnomad4 AFR exome

AF:

0.00241

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.0253

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.00795

Gnomad4 FIN exome

AF:

0.0227

Gnomad4 NFE exome

AF:

0.0136

Gnomad4 OTH exome

AF:

0.0146

GnomAD4 genome

AF:

0.0110

AC:

1671

AN:

152286

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

834

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00498

Gnomad4 FIN

AF:

0.0256

Gnomad4 NFE

AF:

0.0140

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.00275

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2018

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over