1-43172087-G-C

Variant names:

• chr1-43172087-G-C
• NM_006824.3:c.32C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_006824.3(EBNA1BP2):​c.32C>G​(p.Ser11Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S11L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EBNA1BP2 NM_006824.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45

Genes affected

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity EBP2_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBNA1BP2	NM_006824.3	c.32C>G	p.Ser11Trp	missense_variant	Exon 1 of 9	ENST00000236051.3	NP_006815.2
CFAP57	NM_001378189.1	c.-386G>C		upstream_gene_variant		ENST00000372492.9	NP_001365118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBNA1BP2	ENST00000236051.3	c.32C>G	p.Ser11Trp	missense_variant	Exon 1 of 9	1	NM_006824.3	ENSP00000236051.2
CFAP57	ENST00000372492.9	c.-386G>C		upstream_gene_variant		5	NM_001378189.1	ENSP00000361570.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461862 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.83	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.27
Sift	Benign	0.034	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		1.0	.;D
Vest4		0.47
MutPred		0.26		.;Loss of phosphorylation at S11 (P = 0.0014);
MVP		0.84
MPC		1.3
ClinPred		0.91	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.25

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-43637758;