Genetic Variant CFAP97:p.Thr499Met (chr4-185162901-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020827.3(CFAP97):c.1496C>T(p.Thr499Met) variant causes a missense change. The variant allele was found at a frequency of 0.00198 in 1,589,346 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 25 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 27 hom. )

Consequence

CFAP97
NM_020827.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.08

Publications

2 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042895377).

BP6

Variant 4-185162901-G-A is Benign according to our data. Variant chr4-185162901-G-A is described in ClinVar as [Benign]. Clinvar id is 789580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0102 (1546/152294) while in subpopulation AFR AF = 0.0349 (1451/41542). AF 95% confidence interval is 0.0334. There are 25 homozygotes in GnomAd4. There are 755 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP97	NM_020827.3 link	c.1496C>T	p.Thr499Met	missense_variant	Exon 5 of 5	ENST00000458385.7	NP_065878.1	Q9P2B7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP97	ENST00000458385.7 link	c.1496C>T	p.Thr499Met	missense_variant	Exon 5 of 5	2	NM_020827.3	ENSP00000409964.2		Q9P2B7-1

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1542

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0349

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00264

AC:

587

AN:

222392

AF XY:

0.00208

show subpopulations

Gnomad AFR exome

AF:

0.0341

Gnomad AMR exome

AF:

0.00253

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000163

Gnomad OTH exome

AF:

0.00243

GnomAD4 exome

AF:

0.00111

AC:

1601

AN:

1437052

Hom.:

Cov.:

AF XY:

0.000940

AC XY:

671

AN XY:

713490

show subpopulations

African (AFR)

AF:

0.0377

AC:

1213

AN:

32172

American (AMR)

AF:

0.00301

AC:

114

AN:

37910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24866

East Asian (EAS)

AF:

0.00

AC:

AN:

39310

South Asian (SAS)

AF:

0.0000615

AC:

AN:

81330

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53012

Middle Eastern (MID)

AF:

0.00229

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.000102

AC:

113

AN:

1103448

Other (OTH)

AF:

0.00241

AC:

143

AN:

59326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

147

220

294

367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0102

AC:

1546

AN:

152294

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

755

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0349

AC:

1451

AN:

41542

American (AMR)

AF:

0.00451

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68034

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

153

230

306

383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00378

Hom.:

Bravo

AF:

0.0114

ESP6500AA

AF:

0.0336

AC:

128

ESP6500EA

AF:

0.000363

AC:

ExAC

AF:

0.00306

AC:

370

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.2

PhyloP100

4.1

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.97

REVEL

Benign

0.14

Sift

Benign

0.13

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.19

MVP

0.58

MPC

0.13

ClinPred

0.023

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.057

gMVP

0.43

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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4-185162901-G-A

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