Genetic Variant CFAP57:p.His443His (chr1-43198547-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001378189.1(CFAP57):c.1329C>T(p.His443His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,613,696 control chromosomes in the GnomAD database, including 62,656 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5521 hom., cov: 32)

Exomes 𝑓: 0.27 ( 57135 hom. )

Consequence

CFAP57
NM_001378189.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.01

Publications

19 publications found

Variant links:

Genes affected

CFAP57 (HGNC:26485): (cilia and flagella associated protein 57) This protein encoded by this gene belongs to the WD repeat-containing family of proteins, which function in the formation of protein-protein complexes in a variety of biological pathways. This family member is thought to function in craniofacial development, possibly in the fusion of lip and palate. A missense mutation in this gene is associated with Van der Woude syndrome 2. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

CFAP57 links:

EBNA1BP2 (HGNC:15531): (EBNA1 binding protein 2) Enables RNA binding activity. Predicted to be involved in rRNA processing and ribosomal large subunit biogenesis. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

EBNA1BP2 links:

LOC105378685 (HGNC:):

LOC105378685 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP7

Synonymous conserved (PhyloP=2.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP57	NM_001378189.1 link	c.1329C>T	p.His443His	synonymous_variant	Exon 8 of 23	ENST00000372492.9	NP_001365118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP57	ENST00000372492.9 link	c.1329C>T	p.His443His	synonymous_variant	Exon 8 of 23	5	NM_001378189.1	ENSP00000361570.4		Q96MR6-1

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39879

AN:

151996

Hom.:

5510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.325

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.269

GnomAD2 exomes

AF:

0.249

AC:

62654

AN:

251218

AF XY:

0.253

show subpopulations

Gnomad AFR exome

AF:

0.253

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.000489

Gnomad FIN exome

AF:

0.301

Gnomad NFE exome

AF:

0.295

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.275

AC:

401284

AN:

1461582

Hom.:

57135

Cov.:

AF XY:

0.274

AC XY:

199226

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.253

AC:

8466

AN:

33474

American (AMR)

AF:

0.204

AC:

9130

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

7863

AN:

26134

East Asian (EAS)

AF:

0.000529

AC:

AN:

39688

South Asian (SAS)

AF:

0.232

AC:

20026

AN:

86250

European-Finnish (FIN)

AF:

0.298

AC:

15932

AN:

53376

Middle Eastern (MID)

AF:

0.300

AC:

1732

AN:

5768

European-Non Finnish (NFE)

AF:

0.290

AC:

322277

AN:

1111784

Other (OTH)

AF:

0.262

AC:

15837

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

15630

31260

46890

62520

78150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10520

21040

31560

42080

52600

<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:

0.262

AC:

39923

AN:

152114

Hom.:

5521

Cov.:

AF XY:

0.259

AC XY:

19283

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.259

AC:

10731

AN:

41488

American (AMR)

AF:

0.217

AC:

3319

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

1084

AN:

3472

East Asian (EAS)

AF:

0.00193

AC:

AN:

5182

South Asian (SAS)

AF:

0.193

AC:

933

AN:

4822

European-Finnish (FIN)

AF:

0.305

AC:

3223

AN:

10568

Middle Eastern (MID)

AF:

0.336

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.291

AC:

19769

AN:

67974

Other (OTH)

AF:

0.266

AC:

561

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1501

3002

4502

6003

7504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.278

Hom.:

18380

Bravo

AF:

0.257

Asia WGS

AF:

0.121

AC:

424

AN:

3478

EpiCase

AF:

0.292

EpiControl

AF:

0.288

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

2.0

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over