Variant 2-219013954-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_194302.4(CFAP65):c.3693C>T(p.Arg1231Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,613,610 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 13 hom. )

Consequence

CFAP65
NM_194302.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.99

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 2-219013954-G-A is Benign according to our data. Variant chr2-219013954-G-A is described in ClinVar as [Benign]. Clinvar id is 791890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.99 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00546 (832/152320) while in subpopulation AFR AF= 0.0187 (779/41570). AF 95% confidence interval is 0.0176. There are 11 homozygotes in gnomad4. There are 365 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP65	NM_194302.4 linkuse as main transcript	c.3693C>T	p.Arg1231Arg	synonymous_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.3693C>T	p.Arg1231Arg	synonymous_variant	22/35	5	NM_194302.4	ENSP00000340776.5	Q6ZU64-1
CFAP65	ENST00000453220.5 linkuse as main transcript	c.3693C>T	p.Arg1231Arg	synonymous_variant	20/33	5		ENSP00000409117.1	Q6ZU64-1
ENSG00000224090	ENST00000441450.1 linkuse as main transcript	n.225G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00545

AC:

829

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0187

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00146

AC:

365

AN:

249302

Hom.:

AF XY:

0.00109

AC XY:

147

AN XY:

135036

show subpopulations

Gnomad AFR exome

AF:

0.0205

Gnomad AMR exome

AF:

0.000756

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000986

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000558

AC:

815

AN:

1461290

Hom.:

Cov.:

AF XY:

0.000453

AC XY:

329

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.0210

Gnomad4 AMR exome

AF:

0.000762

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.000994

GnomAD4 genome

AF:

0.00546

AC:

832

AN:

152320

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

365

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0187

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00252

Hom.:

Bravo

AF:

0.00641

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.45

DANN

Benign

0.78

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