Variant 7-27245957-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001989.5(EVX1):c.756C>A(p.Asp252Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,609,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

EVX1
NM_001989.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

Variant links:

Genes affected

EVX1 (HGNC:3506): (even-skipped homeobox 1) This gene encodes a member of the even-skipped homeobox family characterized by the presence of a homeodomain closely related to the Drosophila even-skipped (eve) segmentation gene of the pair-rule class. The encoded protein may play an important role as a transcriptional repressor during embryogenesis. [provided by RefSeq, Jul 2008]

EVX1 links:

EVX1-AS (HGNC:40223): (EVX1 antisense RNA) Predicted to enable chromatin binding activity. Predicted to be part of histone methyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

EVX1-AS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05486062).

BS2

High AC in GnomAd4 at 58 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EVX1	NM_001989.5 linkuse as main transcript	c.756C>A	p.Asp252Glu	missense_variant	3/3	ENST00000496902.7
EVX1-AS	NR_120507.1 linkuse as main transcript	n.269+1004G>T		intron_variant, non_coding_transcript_variant
EVX1	NM_001304519.2 linkuse as main transcript	c.210C>A	p.Asp70Glu	missense_variant	3/3
EVX1	NM_001304520.2 linkuse as main transcript	c.210C>A	p.Asp70Glu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVX1	ENST00000496902.7 linkuse as main transcript	c.756C>A	p.Asp252Glu	missense_variant	3/3	1	NM_001989.5	P1	P49640-1
EVX1	ENST00000222761.7 linkuse as main transcript	c.*95C>A		3_prime_UTR_variant	3/3	1
EVX1-AS	ENST00000517726.1 linkuse as main transcript	n.269+1004G>T		intron_variant, non_coding_transcript_variant		3
EVX1	ENST00000580535.1 linkuse as main transcript	c.*95C>A		3_prime_UTR_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.0373

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:

0.000323

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000252

AC:

AN:

242268

Hom.:

AF XY:

0.000279

AC XY:

AN XY:

132586

show subpopulations

Gnomad AFR exome

AF:

0.0000651

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000363

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000205

AC:

299

AN:

1456916

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

168

AN XY:

725068

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000381

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0000481

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:

0.000323

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000233

Hom.:

Bravo

AF:

0.000461

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000415

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

Jan 26, 2022

The c.756C>A (p.D252E) alteration is located in exon 3 (coding exon 3) of the EVX1 gene. This alteration results from a C to A substitution at nucleotide position 756, causing the aspartic acid (D) at amino acid position 252 to be replaced by a glutamic acid (E). 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

Pathogenic

0.94

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.055

MetaSVM

Uncertain

0.79

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.56

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.69

MutPred

0.31

Gain of glycosylation at P250 (P = 0.1104);

MVP

0.93

MPC

1.0

ClinPred

0.45

GERP RS

4.3

Varity_R

0.77

gMVP

0.77

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