rs663824

chr1-43183837-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378189.1(CFAP57):c.721A>G(p.Asn241Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,613,802 control chromosomes in the GnomAD database, including 147,736 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.51 (22146 hom., cov: 32)
  • Exomes 𝑓: 0.41 (125590 hom.)
• Consequence: CFAP57 NM_001378189.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635

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]

LOC105378685 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.7566837E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP57	NM_001378189.1	c.721A>G	p.Asn241Asp	missense_variant	4/23	ENST00000372492.9
LOC105378685	XR_007066041.1	n.670-2053T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP57	ENST00000372492.9	c.721A>G	p.Asn241Asp	missense_variant	4/23	5	NM_001378189.1	P1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77684 AN: 151914 Hom.: 22098 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.473

GnomAD3 exomes AF: 0.445 AC: 111671 AN: 250912 Hom.: 26317 AF XY: 0.437 AC XY: 59278 AN XY: 135606

Gnomad AFR exome AF: 0.779

Gnomad AMR exome AF: 0.521

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.279

Gnomad SAS exome AF: 0.446

Gnomad FIN exome AF: 0.450

Gnomad NFE exome AF: 0.400

Gnomad OTH exome AF: 0.430

GnomAD4 exome AF: 0.408 AC: 596340 AN: 1461772 Hom.: 125590 Cov.: 52 AF XY: 0.408 AC XY: 296492 AN XY: 727198

Gnomad4 AFR exome AF: 0.790

Gnomad4 AMR exome AF: 0.517

Gnomad4 ASJ exome AF: 0.447

Gnomad4 EAS exome AF: 0.259

Gnomad4 SAS exome AF: 0.446

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.512 AC: 77793 AN: 152030 Hom.: 22146 Cov.: 32 AF XY: 0.511 AC XY: 37983 AN XY: 74320

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.470

Alfa AF: 0.414 Hom.: 35278

Bravo AF: 0.523

TwinsUK AF: 0.385 AC: 1428

ALSPAC AF: 0.379 AC: 1460

ESP6500AA AF: 0.758 AC: 3338

ESP6500EA AF: 0.395 AC: 3397

ExAC AF: 0.449 AC: 54522

Asia WGS AF: 0.369 AC: 1283 AN: 3478

EpiCase AF: 0.396

EpiControl AF: 0.393

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.13
Dann	Benign	0.45
DEOGEN2	Benign	0.0018	T;.;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.12	T;T;T
MetaRNN	Benign	0.0000018	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.71	N;N;.
REVEL	Benign	0.016
Sift	Benign	0.45	T;T;.
Sift4G	Benign	0.79	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.014
MPC		0.17
ClinPred		0.0055	T
GERP RS		-3.6
Varity_R		0.037
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs663824; hg19: chr1-43649508; COSMIC: COSV65263622; COSMIC: COSV65263622;