rs621559

Variant names:

• chr1-43179740-G-A
• rs621559
• NM_001378189.1:c.158-1794G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378189.1(CFAP57):​c.158-1794G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 151,934 control chromosomes in the GnomAD database, including 3,271 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 0.18 (3271 hom., cov: 31)
• Consequence: CFAP57 NM_001378189.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858
• Publications: 22 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP57	NM_001378189.1	c.158-1794G>A		intron_variant	Intron 2 of 22	ENST00000372492.9	NP_001365118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP57	ENST00000372492.9	c.158-1794G>A		intron_variant	Intron 2 of 22	5	NM_001378189.1	ENSP00000361570.4

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26557 AN: 151816 Hom.: 3263 Cov.: 31

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.0654

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.132

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.175 AC: 26603 AN: 151934 Hom.: 3271 Cov.: 31 AF XY: 0.181 AC XY: 13430 AN XY: 74268

African (AFR) AF: 0.326 AC: 13498 AN: 41374

American (AMR) AF: 0.221 AC: 3374 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0654 AC: 227 AN: 3470

East Asian (EAS) AF: 0.289 AC: 1487 AN: 5142

South Asian (SAS) AF: 0.209 AC: 1004 AN: 4812

European-Finnish (FIN) AF: 0.148 AC: 1564 AN: 10560

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0757 AC: 5144 AN: 67986

Other (OTH) AF: 0.134 AC: 282 AN: 2110

Alfa AF: 0.107 Hom.: 6393

Bravo AF: 0.185

Asia WGS AF: 0.233 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
DANN	Benign	0.83
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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: rs621559; hg19: chr1-43645411;