Variant 1-155066988-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_005227.3(EFNA4):c.372C>T(p.Phe124=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00507 in 1,612,832 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 41 hom. )

Consequence

EFNA4
NM_005227.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.06

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 1-155066988-C-T is Benign according to our data. Variant chr1-155066988-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 710307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.06 with no splicing effect.

BS2

High AC in GnomAd4 at 685 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EFNA4	NM_005227.3 linkuse as main transcript	c.372C>T	p.Phe124=	synonymous_variant	2/4	ENST00000368409.8	NP_005218.1
EFNA4-EFNA3	NM_001407761.1 linkuse as main transcript	c.113+3052C>T		intron_variant			NP_001394690.1
ADAM15-EFNA4	NR_176418.1 linkuse as main transcript	n.3809C>T		non_coding_transcript_exon_variant	24/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFNA4	ENST00000368409.8 linkuse as main transcript	c.372C>T	p.Phe124=	synonymous_variant	2/4	1	NM_005227.3	ENSP00000357394		P52798-1
EFNA4	ENST00000359751.8 linkuse as main transcript	c.372C>T	p.Phe124=	synonymous_variant	2/4	1		ENSP00000352789	P2	P52798-2
EFNA4	ENST00000427683.2 linkuse as main transcript	c.372C>T	p.Phe124=	synonymous_variant	2/4	2		ENSP00000414378	A2	P52798-3

Frequencies

GnomAD3 genomes

AF:

0.00450

AC:

685

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0169

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00528

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00464

AC:

1160

AN:

249734

Hom.:

AF XY:

0.00472

AC XY:

637

AN XY:

135004

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.00216

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00389

Gnomad FIN exome

AF:

0.0140

Gnomad NFE exome

AF:

0.00552

Gnomad OTH exome

AF:

0.00477

GnomAD4 exome

AF:

0.00512

AC:

7484

AN:

1460512

Hom.:

Cov.:

AF XY:

0.00512

AC XY:

3721

AN XY:

726482

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.0000768

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00363

Gnomad4 FIN exome

AF:

0.0160

Gnomad4 NFE exome

AF:

0.00536

Gnomad4 OTH exome

AF:

0.00403

GnomAD4 genome

AF:

0.00450

AC:

685

AN:

152320

Hom.:

Cov.:

AF XY:

0.00483

AC XY:

360

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0169

Gnomad4 NFE

AF:

0.00528

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00445

Hom.:

Bravo

AF:

0.00314

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00463

EpiControl

AF:

0.00445

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	EFNA4: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 18, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.2

DANN

Benign

0.82

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over