dbSNP rs143886639: EFNA4:p.Pro117Thr (chr1-155066965-C-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3BP4_ModerateBP6_ModerateBS2

The NM_182689.2(EFNA4):c.349C>A(p.Pro117Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000899 in 1,613,978 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 1 hom. )

Consequence

EFNA4
NM_182689.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.01

Publications

10 publications found

Variant links:

Genes affected

EFNA4 (HGNC:3224): (ephrin A4) This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, especially in the nervous system and in erythropoiesis. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. This gene encodes an EFNA class ephrin that has been implicated in proliferation and metastasis of several types of cancers. [provided by RefSeq, May 2022]

EFNA4 links:

EFNA4-EFNA3 (HGNC:):

EFNA4-EFNA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, PROVEAN, REVEL, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.13312006).

BP6

Variant 1-155066965-C-A is Benign according to our data. Variant chr1-155066965-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2061796.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 158 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182689.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EFNA4	NM_005227.3	MANE Select	c.349C>A	p.Pro117Thr	missense	Exon 2 of 4	NP_005218.1
EFNA4	NM_182689.2		c.349C>A	p.Pro117Thr	missense	Exon 2 of 4	NP_872631.1
EFNA4	NM_182690.3		c.349C>A	p.Pro117Thr	missense	Exon 2 of 4	NP_872632.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EFNA4	ENST00000368409.8	TSL:1 MANE Select	c.349C>A	p.Pro117Thr	missense	Exon 2 of 4	ENSP00000357394.3
EFNA4	ENST00000359751.8	TSL:1	c.349C>A	p.Pro117Thr	missense	Exon 2 of 4	ENSP00000352789.4
EFNA4-EFNA3	ENST00000505139.1	TSL:2	c.113+3029C>A		intron	N/A	ENSP00000426741.1

Frequencies

GnomAD3 genomes

AF:

0.00104

AC:

158

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00153

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000996

AC:

250

AN:

251128

AF XY:

0.000906

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00448

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000885

AC:

1293

AN:

1461614

Hom.:

Cov.:

AF XY:

0.000840

AC XY:

611

AN XY:

727098

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33468

American (AMR)

AF:

0.000358

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00540

AC:

288

AN:

53320

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000842

AC:

936

AN:

1111922

Other (OTH)

AF:

0.000778

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

158

236

315

394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

150

<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:

0.00104

AC:

158

AN:

152364

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41588

American (AMR)

AF:

0.000327

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00405

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00153

AC:

104

AN:

68042

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00109

Hom.:

Bravo

AF:

0.000529

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00110

AC:

134

EpiCase

AF:

0.000872

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.88

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.13

MetaSVM

Uncertain

0.38

MutationAssessor

Pathogenic

3.5

PhyloP100

5.0

PROVEAN

Pathogenic

-6.9

REVEL

Pathogenic

0.84

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.91

MVP

0.97

MPC

1.5

ClinPred

0.32

GERP RS

5.3

Varity_R

0.81

gMVP

0.67

Mutation Taster

=18/82

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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