dbSNP rs16990748: 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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Genomics England PanelApp, Orphanet, Ambry Genetics

EFNB1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004429.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004429.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFNB1	NM_004429.5	MANE Select	c.*732A>C		3_prime_UTR	Exon 5 of 5	NP_004420.1	P98172

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFNB1	ENST00000204961.5	TSL:1 MANE Select	c.*732A>C		3_prime_UTR	Exon 5 of 5	ENSP00000204961.4	P98172
	EFNB1	ENST00000851101.1		c.*732A>C		3_prime_UTR	Exon 4 of 4	ENSP00000521160.1

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over