Variant 1-155067373-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_005227.3(EFNA4):c.402G>A(p.Ser134=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000561 in 1,614,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 1 hom. )

Consequence

EFNA4
NM_005227.3 splice_region, synonymous

Scores

Splicing: ADA: 0.0003903

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.67

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 1-155067373-G-A is Benign according to our data. Variant chr1-155067373-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2071464.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 78 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EFNA4	NM_005227.3 linkuse as main transcript	c.402G>A	p.Ser134=	splice_region_variant, synonymous_variant	3/4	ENST00000368409.8	NP_005218.1
EFNA4-EFNA3	NM_001407761.1 linkuse as main transcript	c.113+3437G>A		intron_variant			NP_001394690.1
ADAM15-EFNA4	NR_176418.1 linkuse as main transcript	n.3839G>A		splice_region_variant, non_coding_transcript_exon_variant	25/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFNA4	ENST00000368409.8 linkuse as main transcript	c.402G>A	p.Ser134=	splice_region_variant, synonymous_variant	3/4	1	NM_005227.3	ENSP00000357394		P52798-1
EFNA4	ENST00000359751.8 linkuse as main transcript	c.402G>A	p.Ser134=	splice_region_variant, synonymous_variant	3/4	1		ENSP00000352789	P2	P52798-2
EFNA4	ENST00000427683.2 linkuse as main transcript	c.402G>A	p.Ser134=	splice_region_variant, synonymous_variant	3/4	2		ENSP00000414378	A2	P52798-3

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000660

AC:

166

AN:

251426

Hom.:

AF XY:

0.000692

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000785

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000566

AC:

828

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

391

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.000880

Gnomad4 NFE exome

AF:

0.000657

Gnomad4 OTH exome

AF:

0.000646

GnomAD4 genome

AF:

0.000512

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000851

Hom.:

Bravo

AF:

0.000461

EpiCase

AF:

0.000327

EpiControl

AF:

0.000652

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00039

dbscSNV1_RF

Benign

0.028

SpliceAI score (max)

0.60

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.60

Position offset: 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