16-75395118-C-G

Variant names:

• chr16-75395118-C-G
• rs142200520
• NM_006324.3:c.622G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 17/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.416
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016706705).

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.622G>C	p.Ala208Pro	missense	Exon 5 of 7	NP_006315.1	Q9UEE9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFDP1	ENST00000283882.4	TSL:1 MANE Select	c.622G>C	p.Ala208Pro	missense	Exon 5 of 7	ENSP00000283882.3	Q9UEE9-1
	CFDP1	ENST00000566901.5	TSL:1	n.731G>C		non_coding_transcript_exon	Exon 5 of 5
	CFDP1	ENST00000862206.1		c.745G>C	p.Ala249Pro	missense	Exon 6 of 8	ENSP00000532265.1

Frequencies

GnomAD3 genomes AF: 0.000500 AC: 76 AN: 152094 Hom.: 0 Cov.: 30

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

GnomAD2 exomes AF: 0.000441 AC: 111 AN: 251470 AF XY: 0.000464

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 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.: 1 Cov.: 30 AF XY: 0.000769 AC XY: 559 AN XY: 727146

African (AFR) AF: 0.000149 AC: 5 AN: 33474

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.000749 AC: 40 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000956 AC: 1063 AN: 1111888

Other (OTH) AF: 0.000547 AC: 33 AN: 60380

GnomAD4 genome AF: 0.000499 AC: 76 AN: 152212 Hom.: 0 Cov.: 30 AF XY: 0.000524 AC XY: 39 AN XY: 74406

African (AFR) AF: 0.000145 AC: 6 AN: 41514

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000970 AC: 66 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000820 Hom.: 0

Bravo AF: 0.000495

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000527 AC: 64

EpiCase AF: 0.000763

EpiControl AF: 0.000652

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.035	N
PhyloP100		-0.42
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.068
Sift	Benign	0.27	T
Sift4G	Benign	0.19	T
Polyphen		0.0010	B
Vest4		0.23
MVP		0.41
MPC		0.014
ClinPred		0.0050	T
GERP RS		-0.91
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.041
gMVP		0.34
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs142200520; hg19: chr16-75429016;