dbSNP rs148289726: EFNA4:p.His60Asn (chr1-155066794-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_005227.3(EFNA4):c.178C>A(p.His60Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,612,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H60Y) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

EFNA4
NM_005227.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.68

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.843

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNA4	NM_005227.3 link	c.178C>A	p.His60Asn	missense_variant	Exon 2 of 4	ENST00000368409.8	NP_005218.1	P52798-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EFNA4	ENST00000368409.8 link	c.178C>A	p.His60Asn	missense_variant	Exon 2 of 4	1	NM_005227.3	ENSP00000357394.3	P52798-1
EFNA4	ENST00000359751.8 link	c.178C>A	p.His60Asn	missense_variant	Exon 2 of 4	1		ENSP00000352789.4	P52798-2
EFNA4-EFNA3	ENST00000505139.1 link	c.113+2858C>A		intron_variant	Intron 1 of 4	2		ENSP00000426741.1	B4DXG7
EFNA4	ENST00000427683.2 link	c.178C>A	p.His60Asn	missense_variant	Exon 2 of 4	2		ENSP00000414378.2	P52798-3

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

249144

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

134972

show subpopulations

Gnomad AFR exome

AF:

0.000495

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1460372

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726592

show subpopulations

Gnomad4 AFR exome

AF:

0.000450

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000113

ExAC

AF:

0.0000412

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.85

D;.;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.84

D;D;D

MetaSVM

Pathogenic

0.93

MutationAssessor

Pathogenic

3.3

M;M;M

PROVEAN

Pathogenic

-6.7

D;D;D

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.85

MutPred

0.67

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.98

MPC

1.5

ClinPred

0.89

GERP RS

5.3

Varity_R

0.85

gMVP

0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over