Genetic Variant CFAP97:p.Leu421Leu (chr4-185175843-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020827.3(CFAP97):c.1263A>G(p.Leu421Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,614,002 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 20 hom. )

Consequence

CFAP97
NM_020827.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.961

Publications

1 publications found

Variant links:

Genes affected

CFAP97 (HGNC:29276): (cilia and flagella associated protein 97)

CFAP97 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 4-185175843-T-C is Benign according to our data. Variant chr4-185175843-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3387892.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.961 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP97	NM_020827.3 link	c.1263A>G	p.Leu421Leu	synonymous_variant	Exon 3 of 5	ENST00000458385.7	NP_065878.1	Q9P2B7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CFAP97	ENST00000458385.7 link	c.1263A>G	p.Leu421Leu	synonymous_variant	Exon 3 of 5	2	NM_020827.3	ENSP00000409964.2	Q9P2B7-1
CFAP97	ENST00000514798.1 link	c.1263A>G	p.Leu421Leu	synonymous_variant	Exon 3 of 4	1		ENSP00000423312.1	Q9P2B7-2
CFAP97	ENST00000502992.1 link	n.551A>G		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.00286

AC:

435

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00489

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00284

AC:

708

AN:

249206

AF XY:

0.00266

show subpopulations

Gnomad AFR exome

AF:

0.000904

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00455

Gnomad NFE exome

AF:

0.00479

Gnomad OTH exome

AF:

0.00314

GnomAD4 exome

AF:

0.00367

AC:

5366

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

2644

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33480

American (AMR)

AF:

0.000850

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000459

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000220

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00502

AC:

268

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00436

AC:

4843

AN:

1111842

Other (OTH)

AF:

0.00280

AC:

169

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

277

554

832

1109

1386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00286

AC:

435

AN:

152328

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

198

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000938

AC:

AN:

41580

American (AMR)

AF:

0.000915

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00405

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00489

AC:

333

AN:

68032

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00458

Hom.:

Bravo

AF:

0.00241

EpiCase

AF:

0.00371

EpiControl

AF:

0.00403

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CFAP97: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.29

(source)

DANN

Benign

0.60

PhyloP100

-0.96

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr4-185175843-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over