Variant 2-219013946-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_194302.4(CFAP65):c.3701A>G(p.Asp1234Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00416 in 1,613,880 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 32 hom. )

Consequence

CFAP65
NM_194302.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.90

Variant links:

Genes affected

CFAP65 (HGNC:25325): (cilia and flagella associated protein 65) The protein encoded by this gene has putative coiled-coil domains and may be a transmembrane protein. The chicken ortholog of this gene is involved in the Rose-comb mutation, which is a large chromosome inversion, resulting in altered comb morphology and defects in sperm motility. [provided by RefSeq, Aug 2016]

CFAP65 links:

ENSG00000224090 (HGNC:):

ENSG00000224090 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0083634555).

BP6

Variant 2-219013946-T-C is Benign according to our data. Variant chr2-219013946-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2651905.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00329 (501/152310) while in subpopulation NFE AF= 0.00381 (259/68020). AF 95% confidence interval is 0.00343. There are 3 homozygotes in gnomad4. There are 272 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP65	NM_194302.4 linkuse as main transcript	c.3701A>G	p.Asp1234Gly	missense_variant	22/35	ENST00000341552.10	NP_919278.2	Q6ZU64-1B4DZ05

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CFAP65	ENST00000341552.10 linkuse as main transcript	c.3701A>G	p.Asp1234Gly	missense_variant	22/35	5	NM_194302.4	ENSP00000340776.5	Q6ZU64-1
CFAP65	ENST00000453220.5 linkuse as main transcript	c.3701A>G	p.Asp1234Gly	missense_variant	20/33	5		ENSP00000409117.1	Q6ZU64-1
ENSG00000224090	ENST00000441450.1 linkuse as main transcript	n.217T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00329

AC:

501

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0175

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00381

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00426

AC:

1065

AN:

250138

Hom.:

AF XY:

0.00436

AC XY:

591

AN XY:

135444

show subpopulations

Gnomad AFR exome

AF:

0.000928

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.000998

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0170

Gnomad NFE exome

AF:

0.00582

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00425

AC:

6205

AN:

1461570

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

3025

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.000880

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0148

Gnomad4 NFE exome

AF:

0.00467

Gnomad4 OTH exome

AF:

0.00265

GnomAD4 genome

AF:

0.00329

AC:

501

AN:

152310

Hom.:

Cov.:

AF XY:

0.00365

AC XY:

272

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0175

Gnomad4 NFE

AF:

0.00381

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00367

Hom.:

Bravo

AF:

0.00232

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00470

AC:

571

Asia WGS

AF:

0.000577

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

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

CFAP65: BS1:Supporting -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.69

.;T

MetaRNN

Benign

0.0084

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-6.0

D;D

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.60

MVP

0.75

MPC

0.48

ClinPred

0.043

GERP RS

4.9

Varity_R

0.78

gMVP

0.81

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