1-43222879-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=0.005825013).
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 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 GnomAdExome4. There are 9221 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

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.2588T>C	p.Ile863Thr	missense	Exon 16 of 23	NP_001365118.1
	CFAP57	NM_001195831.3		c.2588T>C	p.Ile863Thr	missense	Exon 16 of 24	NP_001182760.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP57	ENST00000372492.9	TSL:5 MANE Select	c.2588T>C	p.Ile863Thr	missense	Exon 16 of 23	ENSP00000361570.4
	CFAP57	ENST00000610710.4	TSL:5	c.2588T>C	p.Ile863Thr	missense	Exon 16 of 24	ENSP00000479773.1
	EBNA1BP2	ENST00000461557.2	TSL:5	n.109-7486A>G		intron	N/A

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

GnomAD2 exomes AF: 0.00909 AC: 1352 AN: 148734 AF XY: 0.00931

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 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

African (AFR) AF: 0.00219 AC: 69 AN: 31536

American (AMR) AF: 0.00623 AC: 222 AN: 35624

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 478 AN: 25158

East Asian (EAS) AF: 0.00 AC: 0 AN: 35680

South Asian (SAS) AF: 0.00371 AC: 294 AN: 79162

European-Finnish (FIN) AF: 0.00516 AC: 249 AN: 48232

Middle Eastern (MID) AF: 0.0104 AC: 59 AN: 5694

European-Non Finnish (NFE) AF: 0.0159 AC: 17183 AN: 1078508

Other (OTH) AF: 0.0129 AC: 750 AN: 57966

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

African (AFR) AF: 0.00308 AC: 128 AN: 41492

American (AMR) AF: 0.00988 AC: 151 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00396 AC: 19 AN: 4794

European-Finnish (FIN) AF: 0.00359 AC: 38 AN: 10582

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0155 AC: 1055 AN: 67960

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.0136 Hom.: 30

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 v4.9

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
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.1	T
PhyloP100		5.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.098
Sift	Uncertain	0.010	D
Sift4G	Benign	0.35	T
Vest4		0.34
MVP		0.14
ClinPred		0.020	T
GERP RS		4.4
Varity_R		0.21
gMVP		0.18
Mutation Taster		=87/13	polymorphism

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: rs150404479; hg19: chr1-43688550;