Variant 1-155133771-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004428.3(EFNA1):c.496C>T(p.Leu166Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

EFNA1
NM_004428.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.208

Variant links:

Genes affected

EFNA1 (HGNC:3221): (ephrin A1) 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 which binds to the EPHA2, EPHA4, EPHA5, EPHA6, and EPHA7 receptors. Two transcript variants that encode different isoforms were identified through sequence analysis. [provided by RefSeq, Jul 2008]

EFNA1 links:

EFNA1 (HGNC:):

EFNA1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17153513).

BS2

High AC in GnomAdExome4 at 38 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFNA1	NM_004428.3 linkuse as main transcript	c.496C>T	p.Leu166Phe	missense_variant	4/5	ENST00000368407.8	NP_004419.2	P20827-1
EFNA1	NM_182685.2 linkuse as main transcript	c.430C>T	p.Leu144Phe	missense_variant	3/4		NP_872626.1	P20827-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFNA1	ENST00000368407.8 linkuse as main transcript	c.496C>T	p.Leu166Phe	missense_variant	4/5	1	NM_004428.3	ENSP00000357392.3		P20827-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000333

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000227

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2022

The c.496C>T (p.L166F) alteration is located in exon 4 (coding exon 4) of the EFNA1 gene. This alteration results from a C to T substitution at nucleotide position 496, causing the leucine (L) at amino acid position 166 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.082

T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.17

T;T

MetaSVM

Uncertain

0.069

MutationAssessor

Benign

0.97

L;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.87

N;N

REVEL

Benign

0.26

Sift

Benign

0.34

T;T

Sift4G

Benign

0.56

T;D

Polyphen

0.96

D;P

Vest4

0.069

MutPred

0.31

Gain of methylation at K164 (P = 0.0955);.;

MVP

0.68

MPC

0.22

ClinPred

0.44

GERP RS

2.4

Varity_R

0.067

gMVP

0.34

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