rs663824

Variant names:

• chr1-43183837-A-G
• rs663824
• NM_001378189.1:c.721A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 30 publications found

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]

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]

LOC105378685 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378189.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP57	NM_001378189.1	MANE Select	c.721A>G	p.Asn241Asp	missense	Exon 4 of 23	NP_001365118.1
	CFAP57	NM_001195831.3		c.721A>G	p.Asn241Asp	missense	Exon 4 of 24	NP_001182760.2
	CFAP57	NM_001167965.1		c.721A>G	p.Asn241Asp	missense	Exon 4 of 11	NP_001161437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP57	ENST00000372492.9	TSL:5 MANE Select	c.721A>G	p.Asn241Asp	missense	Exon 4 of 23	ENSP00000361570.4
	CFAP57	ENST00000533339.1	TSL:1	n.*620A>G		non_coding_transcript_exon	Exon 5 of 13	ENSP00000432547.1
	CFAP57	ENST00000533339.1	TSL:1	n.*620A>G		3_prime_UTR	Exon 5 of 13	ENSP00000432547.1

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

GnomAD2 exomes AF: 0.445 AC: 111671 AN: 250912 AF XY: 0.437

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 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

African (AFR) AF: 0.790 AC: 26459 AN: 33478

American (AMR) AF: 0.517 AC: 23133 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 11693 AN: 26136

East Asian (EAS) AF: 0.259 AC: 10263 AN: 39698

South Asian (SAS) AF: 0.446 AC: 38434 AN: 86250

European-Finnish (FIN) AF: 0.447 AC: 23852 AN: 53408

Middle Eastern (MID) AF: 0.495 AC: 2843 AN: 5748

European-Non Finnish (NFE) AF: 0.390 AC: 434133 AN: 1111942

Other (OTH) AF: 0.423 AC: 25530 AN: 60390

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

African (AFR) AF: 0.776 AC: 32197 AN: 41484

American (AMR) AF: 0.482 AC: 7361 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1613 AN: 3470

East Asian (EAS) AF: 0.290 AC: 1500 AN: 5166

South Asian (SAS) AF: 0.412 AC: 1987 AN: 4820

European-Finnish (FIN) AF: 0.471 AC: 4968 AN: 10550

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26810 AN: 67956

Other (OTH) AF: 0.470 AC: 993 AN: 2114

Alfa AF: 0.429 Hom.: 74100

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 v4.9

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
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0000018	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.64
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.71	N
REVEL	Benign	0.016
Sift	Benign	0.45	T
Sift4G	Benign	0.79	T
Polyphen		0.0	B
Vest4		0.014
MPC		0.17
ClinPred		0.0055	T
GERP RS		-3.6
Varity_R		0.037
gMVP		0.12
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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