rs147599832

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2

The NM_004429.5(EFNB1):c.509C>T(p.Ala170Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,210,488 control chromosomes in the GnomAD database, including 12 homozygotes. There are 339 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 4 hom., 163 hem., cov: 24)

Exomes 𝑓: 0.00056 ( 8 hom. 176 hem. )

Consequence

EFNB1
NM_004429.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.26

Publications

1 publications found

Variant links:

Genes affected

EFNB1 (HGNC:3226): (ephrin B1) The protein encoded by this gene is a type I membrane protein and a ligand of Eph-related receptor tyrosine kinases. It may play a role in cell adhesion and function in the development or maintenance of the nervous system. [provided by RefSeq, Jul 2008]

EFNB1 Gene-Disease associations (from GenCC):

craniofrontonasal syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

EFNB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

PM1

In a topological_domain Extracellular (size 209) in uniprot entity EFNB1_HUMAN there are 28 pathogenic changes around while only 5 benign (85%) in NM_004429.5

BP4

Computational evidence support a benign effect (MetaRNN=0.0074879825).

BP6

Variant X-68839969-C-T is Benign according to our data. Variant chrX-68839969-C-T is described in ClinVar as Benign. ClinVar VariationId is 376763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00533 (600/112482) while in subpopulation AFR AF = 0.0184 (570/30983). AF 95% confidence interval is 0.0171. There are 4 homozygotes in GnomAd4. There are 163 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNB1	NM_004429.5 link	c.509C>T	p.Ala170Val	missense_variant	Exon 4 of 5	ENST00000204961.5	NP_004420.1	P98172

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFNB1	ENST00000204961.5 link	c.509C>T	p.Ala170Val	missense_variant	Exon 4 of 5	1	NM_004429.5	ENSP00000204961.4		P98172

Frequencies

GnomAD3 genomes

AF:

0.00535

AC:

601

AN:

112429

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00233

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00265

GnomAD2 exomes

AF:

0.00151

AC:

275

AN:

182215

AF XY:

0.00108

show subpopulations

Gnomad AFR exome

AF:

0.0181

Gnomad AMR exome

AF:

0.00132

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.000557

AC:

612

AN:

1098006

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

176

AN XY:

363366

show subpopulations

African (AFR)

AF:

0.0189

AC:

500

AN:

26400

American (AMR)

AF:

0.00142

AC:

AN:

35182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19381

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54065

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40518

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4129

European-Non Finnish (NFE)

AF:

0.00000831

AC:

AN:

842038

Other (OTH)

AF:

0.00115

AC:

AN:

46088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

125

156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00533

AC:

600

AN:

112482

Hom.:

Cov.:

AF XY:

0.00470

AC XY:

163

AN XY:

34650

show subpopulations

African (AFR)

AF:

0.0184

AC:

570

AN:

30983

American (AMR)

AF:

0.00233

AC:

AN:

10742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3545

South Asian (SAS)

AF:

0.00

AC:

AN:

2682

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53243

Other (OTH)

AF:

0.00261

AC:

AN:

1530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00163

Hom.:

Bravo

AF:

0.00701

ESP6500AA

AF:

0.0146

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00188

AC:

228

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 19, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 09, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.22

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0075

MetaSVM

Uncertain

-0.13

MutationAssessor

Uncertain

2.1

PhyloP100

2.3

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.29

Sift

Benign

0.11

Sift4G

Benign

0.49

Polyphen

0.42

Vest4

0.29

MVP

0.87

MPC

0.70

ClinPred

0.025

GERP RS

5.1

Varity_R

0.22

gMVP

0.86

Mutation Taster

=73/27

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over