Variant chr5-74636490-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003633.4(ENC1):c.-5A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,557,942 control chromosomes in the GnomAD database, including 321,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.63 ( 30326 hom., cov: 31)

Exomes 𝑓: 0.64 ( 291575 hom. )

Consequence

ENC1
NM_003633.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.850

Variant links:

Genes affected

ENC1 (HGNC:3345): (ectodermal-neural cortex 1) This gene encodes a member of the kelch-related family of actin-binding proteins. The encoded protein plays a role in the oxidative stress response as a regulator of the transcription factor Nrf2, and expression of this gene may play a role in malignant transformation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ENC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 5-74636490-T-C is Benign according to our data. Variant chr5-74636490-T-C is described in ClinVar as [Benign]. Clinvar id is 1290799.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENC1	NM_003633.4 linkuse as main transcript	c.-5A>G		5_prime_UTR_variant	2/3	ENST00000302351.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENC1	ENST00000302351.9 linkuse as main transcript	c.-5A>G		5_prime_UTR_variant	2/3	1	NM_003633.4	P1	O14682-1

Frequencies

GnomAD3 genomes

AF:

0.630

AC:

95599

AN:

151834

Hom.:

30310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.730

Gnomad ASJ

AF:

0.733

Gnomad EAS

AF:

0.700

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.622

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.646

Gnomad OTH

AF:

0.670

GnomAD3 exomes

AF:

0.657

AC:

153994

AN:

234306

Hom.:

51132

AF XY:

0.653

AC XY:

83308

AN XY:

127586

show subpopulations

Gnomad AFR exome

AF:

0.563

Gnomad AMR exome

AF:

0.767

Gnomad ASJ exome

AF:

0.738

Gnomad EAS exome

AF:

0.699

Gnomad SAS exome

AF:

0.582

Gnomad FIN exome

AF:

0.618

Gnomad NFE exome

AF:

0.653

Gnomad OTH exome

AF:

0.673

GnomAD4 exome

AF:

0.642

AC:

902798

AN:

1405990

Hom.:

291575

Cov.:

AF XY:

0.640

AC XY:

445840

AN XY:

696458

show subpopulations

Gnomad4 AFR exome

AF:

0.557

Gnomad4 AMR exome

AF:

0.756

Gnomad4 ASJ exome

AF:

0.731

Gnomad4 EAS exome

AF:

0.701

Gnomad4 SAS exome

AF:

0.574

Gnomad4 FIN exome

AF:

0.620

Gnomad4 NFE exome

AF:

0.641

Gnomad4 OTH exome

AF:

0.653

GnomAD4 genome

AF:

0.630

AC:

95655

AN:

151952

Hom.:

30326

Cov.:

AF XY:

0.627

AC XY:

46560

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.556

Gnomad4 AMR

AF:

0.730

Gnomad4 ASJ

AF:

0.733

Gnomad4 EAS

AF:

0.699

Gnomad4 SAS

AF:

0.570

Gnomad4 FIN

AF:

0.622

Gnomad4 NFE

AF:

0.646

Gnomad4 OTH

AF:

0.667

Alfa

AF:

0.640

Hom.:

15887

Bravo

AF:

0.640

Asia WGS

AF:

0.625

AC:

2173

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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