Genetic Variant CFDP1:p.Ala60Thr (chr16-75414582-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_006324.3(CFDP1):c.178G>A(p.Ala60Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,603,784 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 22 hom. )

Consequence

CFDP1
NM_006324.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.105

Publications

9 publications found

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:

ENSG00000261717 (HGNC:):

ENSG00000261717 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005605638).

BP6

Variant 16-75414582-C-T is Benign according to our data. Variant chr16-75414582-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3038964.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 22 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006324.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFDP1	NM_006324.3	MANE Select	c.178G>A	p.Ala60Thr	missense	Exon 2 of 7	NP_006315.1	Q9UEE9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFDP1	ENST00000283882.4	TSL:1 MANE Select	c.178G>A	p.Ala60Thr	missense	Exon 2 of 7	ENSP00000283882.3	Q9UEE9-1
ENSG00000261717	ENST00000567194.5	TSL:2	c.349G>A	p.Ala117Thr	missense	Exon 3 of 4	ENSP00000457654.1	H3BUI4
CFDP1	ENST00000566901.5	TSL:1	n.287G>A		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.00370

AC:

563

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00434

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00381

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00335

AC:

841

AN:

251360

AF XY:

0.00330

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.00605

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00337

Gnomad NFE exome

AF:

0.00396

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00372

AC:

5403

AN:

1451528

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

2683

AN XY:

722954

show subpopulations

African (AFR)

AF:

0.00289

AC:

AN:

33266

American (AMR)

AF:

0.00423

AC:

189

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00717

AC:

187

AN:

26064

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39622

South Asian (SAS)

AF:

0.00137

AC:

118

AN:

86052

European-Finnish (FIN)

AF:

0.00346

AC:

185

AN:

53404

Middle Eastern (MID)

AF:

0.00348

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00397

AC:

4380

AN:

1102636

Other (OTH)

AF:

0.00378

AC:

227

AN:

60038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

231

462

692

923

1154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

320

480

640

800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00370

AC:

564

AN:

152256

Hom.:

Cov.:

AF XY:

0.00379

AC XY:

282

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41564

American (AMR)

AF:

0.00739

AC:

113

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00952

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00145

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00434

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00381

AC:

259

AN:

68016

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

122

152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00419

Hom.:

Bravo

AF:

0.00407

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00341

AC:

ESP6500EA

AF:

0.00430

AC:

ExAC

AF:

0.00298

AC:

362

EpiCase

AF:

0.00567

EpiControl

AF:

0.00445

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CFDP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.52

M_CAP

Benign

0.0083

MetaRNN

Benign

0.0056

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

-0.10

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.40

REVEL

Benign

0.068

Sift

Benign

0.31

Sift4G

Benign

0.65

Polyphen

0.0060

Vest4

0.15

MVP

0.49

MPC

0.013

ClinPred

0.0087

GERP RS

2.0

Varity_R

0.028

gMVP

0.032

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over