chr1-43172417-T-C

Variant names:

• chr1-43172417-T-C
• rs781669513
• NM_001378189.1:c.-56T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001159936.1(EBNA1BP2):​c.5A>G​(p.Tyr2Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000035 in 1,399,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: EBNA1BP2 NM_001159936.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0580
• Publications: 3 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07935229).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159936.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP57	NM_001378189.1	MANE Select	c.-56T>C		5_prime_UTR	Exon 1 of 23	NP_001365118.1	Q96MR6-1
	EBNA1BP2	NM_001159936.1		c.5A>G	p.Tyr2Cys	missense	Exon 1 of 10	NP_001153408.1	Q99848
	CFAP57	NM_001195831.3		c.-59T>C		5_prime_UTR	Exon 1 of 24	NP_001182760.2	A0A087WVY5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP57	ENST00000372492.9	TSL:5 MANE Select	c.-56T>C		5_prime_UTR	Exon 1 of 23	ENSP00000361570.4	Q96MR6-1
	EBNA1BP2	ENST00000431635.6	TSL:2	c.5A>G	p.Tyr2Cys	missense	Exon 1 of 10	ENSP00000407323.2	H7C2Q8
	CFAP57	ENST00000610710.4	TSL:5	c.-59T>C		5_prime_UTR	Exon 1 of 24	ENSP00000479773.1	A0A087WVY5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000130 AC: 2 AN: 153830 AF XY: 0.0000123

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000336

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000350 AC: 49 AN: 1399324 Hom.: 0 Cov.: 33 AF XY: 0.0000203 AC XY: 14 AN XY: 690164

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.0000454 AC: 49 AN: 1078958

Other (OTH) AF: 0.00 AC: 0 AN: 57992

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000936 Hom.: 0

ExAC AF: 0.0000357 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.8
DANN	Benign	0.96
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.058
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.013
Sift	Pathogenic	0.0	D
Vest4		0.13
MutPred		0.21		Loss of phosphorylation at Y2 (P = 0.1215)
MVP		0.35
MPC		0.41
ClinPred		0.13	T
GERP RS		0.062
PromoterAI		0.025	Neutral
gMVP		0.051
Mutation Taster		=296/4	polymorphism

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: rs781669513; hg19: chr1-43638088;