Variant 10-22209358-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394757.1(EBLN1):c.626T>A(p.Phe209Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000331 in 1,605,524 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00029 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 1 hom. )

Consequence

EBLN1
NM_001394757.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0160

Variant links:

Genes affected

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

EBLN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009052426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBLN1	NM_001394757.1 linkuse as main transcript	c.626T>A	p.Phe209Tyr	missense_variant	3/3	ENST00000422359.3	NP_001381686.1
EBLN1	NM_001199938.2 linkuse as main transcript	c.626T>A	p.Phe209Tyr	missense_variant	1/1		NP_001186867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBLN1	ENST00000422359.3 linkuse as main transcript	c.626T>A	p.Phe209Tyr	missense_variant	3/3		NM_001394757.1	ENSP00000473842	P1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000609

AC:

141

AN:

231402

Hom.:

AF XY:

0.000517

AC XY:

AN XY:

127592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000729

Gnomad ASJ exome

AF:

0.00871

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000223

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.000336

AC:

488

AN:

1453176

Hom.:

Cov.:

AF XY:

0.000326

AC XY:

236

AN XY:

723104

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00972

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.000289

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.000382

ExAC

AF:

0.000416

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 05, 2021

The c.626T>A (p.F209Y) alteration is located in exon 1 (coding exon 1) of the EBLN1 gene. This alteration results from a T to A substitution at nucleotide position 626, causing the phenylalanine (F) at amino acid position 209 to be replaced by a tyrosine (Y). 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

0.28

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.52

DEOGEN2

Benign

0.0073

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.21

M_CAP

Benign

0.0088

MetaRNN

Benign

0.0091

MutationAssessor

Benign

0.55

PrimateAI

Uncertain

0.53

Sift4G

Benign

0.096

Vest4

0.28

MVP

0.10

MPC

0.79

GERP RS

-1.0

Varity_R

0.21

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over