Genetic Variant EFNB1:c.*732A>C (chrX-68841386-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004429.5(EFNB1):c.*732A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 107,250 control chromosomes in the GnomAD database, including 64 homozygotes. There are 817 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.027 ( 64 hom., 817 hem., cov: 21)

Exomes 𝑓: 0.086 ( 9 hom. 7 hem. )

Failed GnomAD Quality Control

Consequence

EFNB1
NM_004429.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.352

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNB1	NM_004429.5 link	c.*732A>C		3_prime_UTR_variant	Exon 5 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.*732A>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_004429.5	ENSP00000204961.4		P98172

Frequencies

GnomAD3 genomes

AF:

0.0272

AC:

2921

AN:

107209

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0735

Gnomad AMI

AF:

0.00151

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.0200

Gnomad SAS

AF:

0.0403

Gnomad FIN

AF:

0.00969

Gnomad MID

AF:

0.0130

Gnomad NFE

AF:

0.00606

Gnomad OTH

AF:

0.0172

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0861

AC:

AN:

337

Hom.:

Cov.:

AF XY:

0.0483

AC XY:

AN XY:

145

show subpopulations

African (AFR)

AF:

0.800

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.0153

AC:

AN:

261

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.327

AC:

AN:

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0273

AC:

2924

AN:

107250

Hom.:

Cov.:

AF XY:

0.0266

AC XY:

817

AN XY:

30696

show subpopulations

African (AFR)

AF:

0.0734

AC:

2149

AN:

29264

American (AMR)

AF:

0.0147

AC:

151

AN:

10266

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

AN:

2575

East Asian (EAS)

AF:

0.0201

AC:

AN:

3383

South Asian (SAS)

AF:

0.0404

AC:

103

AN:

2547

European-Finnish (FIN)

AF:

0.00969

AC:

AN:

5262

Middle Eastern (MID)

AF:

0.0144

AC:

AN:

209

European-Non Finnish (NFE)

AF:

0.00607

AC:

313

AN:

51607

Other (OTH)

AF:

0.0183

AC:

AN:

1474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

198

298

397

496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.556

Hom.:

2297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.27

(source)

DANN

Benign

0.59

PhyloP100

0.35

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over