10-22209251-C-G

Position:

• chr10-22209251-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394757.1(EBLN1):​c.733G>C​(p.Asp245His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EBLN1 NM_001394757.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.160

Genes affected

EBLN1 (HGNC:39430): (endogenous Bornavirus like nucleoprotein 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11350885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBLN1	NM_001394757.1	c.733G>C	p.Asp245His	missense_variant	3/3	ENST00000422359.3	NP_001381686.1
EBLN1	NM_001199938.2	c.733G>C	p.Asp245His	missense_variant	1/1		NP_001186867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBLN1	ENST00000422359.3	c.733G>C	p.Asp245His	missense_variant	3/3		NM_001394757.1	ENSP00000473842	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

The c.733G>C (p.D245H) alteration is located in exon 1 (coding exon 1) of the EBLN1 gene. This alteration results from a G to C substitution at nucleotide position 733, causing the aspartic acid (D) at amino acid position 245 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.51
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.11	T
MutationAssessor	Benign	0.34	N
PrimateAI	Uncertain	0.50	T
Sift4G	Benign	0.14	T
Vest4		0.19
MVP		0.15
MPC		1.6
GERP RS		-0.53
Varity_R		0.17
gMVP		0.36

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: rs1332781434; hg19: chr10-22498180;