Variant 16-75395118-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006324.3(CFDP1):c.622G>C(p.Ala208Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000758 in 1,613,894 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00078 ( 1 hom. )

Consequence

CFDP1
NM_006324.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.416

Variant links:

Genes affected

CFDP1 (HGNC:1873): (craniofacial development protein 1) Predicted to act upstream of or within several processes, including cell adhesion; negative regulation of fibroblast apoptotic process; and regulation of cell shape. Predicted to be located in kinetochore. [provided by Alliance of Genome Resources, Apr 2022]

CFDP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016706705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFDP1	NM_006324.3 linkuse as main transcript	c.622G>C	p.Ala208Pro	missense_variant	5/7	ENST00000283882.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFDP1	ENST00000283882.4 linkuse as main transcript	c.622G>C	p.Ala208Pro	missense_variant	5/7	1	NM_006324.3	P1	Q9UEE9-1

Frequencies

GnomAD3 genomes

AF:

0.000500

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000441

AC:

111

AN:

251470

Hom.:

AF XY:

0.000464

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.000844

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000785

AC:

1147

AN:

1461682

Hom.:

Cov.:

AF XY:

0.000769

AC XY:

559

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000749

Gnomad4 NFE exome

AF:

0.000956

Gnomad4 OTH exome

AF:

0.000547

GnomAD4 genome

AF:

0.000499

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000970

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000820

Hom.:

Bravo

AF:

0.000495

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000527

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000652

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.622G>C (p.A208P) alteration is located in exon 5 (coding exon 5) of the CFDP1 gene. This alteration results from a G to C substitution at nucleotide position 622, causing the alanine (A) at amino acid position 208 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.023

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.63

M_CAP

Benign

0.0053

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.035

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.48

REVEL

Benign

0.068

Sift

Benign

0.27

Sift4G

Benign

0.19

Polyphen

0.0010

Vest4

0.23

MVP

0.41

MPC

0.014

ClinPred

0.0050

GERP RS

-0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.041

gMVP

0.34

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