Variant 2-219010931-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_194302.4(CFAP65):c.4023A>T(p.Ser1341Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,613,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

CFAP65
NM_194302.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.89

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 -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-219010931-T-A is Benign according to our data. Variant chr2-219010931-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3388517.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.89 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000354 (54/152376) while in subpopulation NFE AF= 0.000514 (35/68036). AF 95% confidence interval is 0.000379. There are 0 homozygotes in gnomad4. There are 33 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP65	NM_194302.4 link	c.4023A>T	p.Ser1341Ser	synonymous_variant	25/35	ENST00000341552.10	NP_919278.2	Q6ZU64-1B4DZ05

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CFAP65	ENST00000341552.10 link	c.4023A>T	p.Ser1341Ser	synonymous_variant	25/35	5	NM_194302.4	ENSP00000340776.5	Q6ZU64-1
CFAP65	ENST00000453220.5 link	c.4023A>T	p.Ser1341Ser	synonymous_variant	23/33	5		ENSP00000409117.1	Q6ZU64-1
ENSG00000224090	ENST00000441450.1 link	n.172+889T>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000251

AC:

AN:

250926

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000878

Gnomad NFE exome

AF:

0.000362

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000210

AC:

307

AN:

1461544

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

151

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00115

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000354

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.000514

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000406

Hom.:

Bravo

AF:

0.000106

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000119

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

Sep 01, 2024

CFAP65: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.041

DANN

Benign

0.66

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