10-22209371-A-C

Variant names:

• chr10-22209371-A-C
• NM_001394757.1:c.613T>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.613T>G​(p.Leu205Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: EBLN1 NM_001394757.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.138

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=0.08303085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBLN1	NM_001394757.1	c.613T>G	p.Leu205Val	missense_variant	Exon 3 of 3	ENST00000422359.3	NP_001381686.1
EBLN1	NM_001199938.2	c.613T>G	p.Leu205Val	missense_variant	Exon 1 of 1		NP_001186867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBLN1	ENST00000422359.3	c.613T>G	p.Leu205Val	missense_variant	Exon 3 of 3	6	NM_001394757.1	ENSP00000473842.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1453310 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 723196

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.613T>G (p.L205V) alteration is located in exon 1 (coding exon 1) of the EBLN1 gene. This alteration results from a T to G substitution at nucleotide position 613, causing the leucine (L) at amino acid position 205 to be replaced by a valine (V). 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	0.19
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Benign	0.82
DEOGEN2	Benign	0.0081	T
FATHMM_MKL	Benign	0.0080	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.083	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.42	T
Sift4G	Benign	0.067	T
Vest4		0.16
MVP		0.15
MPC		1.3
GERP RS		0.51
Varity_R		0.17
gMVP		0.083

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr10-22498300;