1-43222879-T-C

Variant names:

• chr1-43222879-T-C
• rs150404479
• NM_001378189.1:c.2588T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001378189.1(CFAP57):​c.2588T>C​(p.Ile863Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0134 in 1,549,630 control chromosomes in the GnomAD database, including 184 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 0.0098 (13 hom., cov: 32)
  • Exomes 𝑓: 0.014 (171 hom.)
• Consequence: CFAP57 NM_001378189.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.09

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005825013).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0138 (19304/1397560) while in subpopulation NFE AF= 0.0159 (17183/1078508). AF 95% confidence interval is 0.0157. There are 171 homozygotes in gnomad4_exome. There are 9221 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1486 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP57	NM_001378189.1	c.2588T>C	p.Ile863Thr	missense_variant	Exon 16 of 23	ENST00000372492.9	NP_001365118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP57	ENST00000372492.9	c.2588T>C	p.Ile863Thr	missense_variant	Exon 16 of 23	5	NM_001378189.1	ENSP00000361570.4

Frequencies

GnomAD3 genomes AF: 0.00979 AC: 1488 AN: 151952 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00309

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00996

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00417

Gnomad FIN AF: 0.00359

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00909 AC: 1352 AN: 148734 Hom.: 13 AF XY: 0.00931 AC XY: 746 AN XY: 80100

Gnomad AFR exome AF: 0.00178

Gnomad AMR exome AF: 0.00573

Gnomad ASJ exome AF: 0.0193

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00298

Gnomad FIN exome AF: 0.00416

Gnomad NFE exome AF: 0.0153

Gnomad OTH exome AF: 0.0147

GnomAD4 exome AF: 0.0138 AC: 19304 AN: 1397560 Hom.: 171 Cov.: 31 AF XY: 0.0134 AC XY: 9221 AN XY: 689310

Gnomad4 AFR exome AF: 0.00219

Gnomad4 AMR exome AF: 0.00623

Gnomad4 ASJ exome AF: 0.0190

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00371

Gnomad4 FIN exome AF: 0.00516

Gnomad4 NFE exome AF: 0.0159

Gnomad4 OTH exome AF: 0.0129

GnomAD4 genome AF: 0.00977 AC: 1486 AN: 152070 Hom.: 13 Cov.: 32 AF XY: 0.00881 AC XY: 655 AN XY: 74324

Gnomad4 AFR AF: 0.00308

Gnomad4 AMR AF: 0.00988

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00396

Gnomad4 FIN AF: 0.00359

Gnomad4 NFE AF: 0.0155

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.0129 Hom.: 10

Bravo AF: 0.0104

TwinsUK AF: 0.0181 AC: 67

ALSPAC AF: 0.0140 AC: 54

ExAC AF: 0.00560 AC: 127

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D;D
MetaRNN	Benign	0.0058	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.1	D;.
REVEL	Benign	0.098
Sift	Uncertain	0.010	D;.
Sift4G	Benign	0.35	T;T
Vest4		0.34
MVP		0.14
ClinPred		0.020	T
GERP RS		4.4
Varity_R		0.21
gMVP		0.18

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: rs150404479; hg19: chr1-43688550;