Genetic Variant NM_001394757.1:c.704T>C (chr10-22209280-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001394757.1(EBLN1):c.704T>C(p.Met235Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,589,788 control chromosomes in the GnomAD database, including 58,483 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8842 hom., cov: 32)

Exomes 𝑓: 0.26 ( 49641 hom. )

Consequence

EBLN1
NM_001394757.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0200

Publications

16 publications found

Variant links:

Genes affected

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

EBLN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.234403E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBLN1	NM_001394757.1 link	c.704T>C	p.Met235Thr	missense_variant	Exon 3 of 3	ENST00000422359.3	NP_001381686.1
EBLN1	NM_001199938.2 link	c.704T>C	p.Met235Thr	missense_variant	Exon 1 of 1		NP_001186867.1	P0CF75

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBLN1	ENST00000422359.3 link	c.704T>C	p.Met235Thr	missense_variant	Exon 3 of 3	6	NM_001394757.1	ENSP00000473842.1		P0CF75

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48913

AN:

152014

Hom.:

8815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.470

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.310

GnomAD2 exomes

AF:

0.258

AC:

54099

AN:

209552

AF XY:

0.248

show subpopulations

Gnomad AFR exome

AF:

0.501

Gnomad AMR exome

AF:

0.279

Gnomad ASJ exome

AF:

0.324

Gnomad EAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.208

Gnomad NFE exome

AF:

0.255

Gnomad OTH exome

AF:

0.258

GnomAD4 exome

AF:

0.258

AC:

370460

AN:

1437656

Hom.:

49641

Cov.:

AF XY:

0.254

AC XY:

181652

AN XY:

714528

show subpopulations

African (AFR)

AF:

0.503

AC:

16797

AN:

33404

American (AMR)

AF:

0.290

AC:

12458

AN:

43018

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

8560

AN:

25962

East Asian (EAS)

AF:

0.184

AC:

7268

AN:

39504

South Asian (SAS)

AF:

0.165

AC:

14011

AN:

85054

European-Finnish (FIN)

AF:

0.209

AC:

7892

AN:

37680

Middle Eastern (MID)

AF:

0.231

AC:

1331

AN:

5758

European-Non Finnish (NFE)

AF:

0.258

AC:

285935

AN:

1107254

Other (OTH)

AF:

0.270

AC:

16208

AN:

60022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

18701

37402

56102

74803

93504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9750

19500

29250

39000

48750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.322

AC:

48989

AN:

152132

Hom.:

8842

Cov.:

AF XY:

0.318

AC XY:

23625

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.495

AC:

20551

AN:

41492

American (AMR)

AF:

0.307

AC:

4690

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

1116

AN:

3468

East Asian (EAS)

AF:

0.205

AC:

1059

AN:

5164

South Asian (SAS)

AF:

0.175

AC:

844

AN:

4828

European-Finnish (FIN)

AF:

0.202

AC:

2139

AN:

10586

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.257

AC:

17448

AN:

67996

Other (OTH)

AF:

0.310

AC:

655

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1656

3313

4969

6626

8282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.274

Hom.:

26086

Bravo

AF:

0.339

TwinsUK

AF:

0.260

AC:

965

ALSPAC

AF:

0.249

AC:

960

ExAC

AF:

0.245

AC:

28961

Asia WGS

AF:

0.268

AC:

932

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.094

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0011

FATHMM_MKL

Benign

0.000090

LIST_S2

Benign

0.16

MetaRNN

Benign

0.000092

MutationAssessor

Benign

-0.69

PhyloP100

-0.020

PrimateAI

Uncertain

0.51

Sift4G

Benign

1.0

Vest4

0.039

MPC

0.63

GERP RS

0.51

Varity_R

0.13

gMVP

0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over