Variant chr5-74634926-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003633.4(ENC1):c.1560G>A(p.Lys520Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 1,613,538 control chromosomes in the GnomAD database, including 331,446 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.63 ( 30121 hom., cov: 32)

Exomes 𝑓: 0.64 ( 301325 hom. )

Consequence

ENC1
NM_003633.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.778

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:

ENC1 (HGNC:):

ENC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP7

Synonymous conserved (PhyloP=0.778 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENC1	NM_003633.4 linkuse as main transcript	c.1560G>A	p.Lys520Lys	synonymous_variant	2/3	ENST00000302351.9	NP_003624.1	O14682-1Q53XS2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ENC1	ENST00000302351.9 linkuse as main transcript	c.1560G>A	p.Lys520Lys	synonymous_variant	2/3	1	NM_003633.4	ENSP00000306356.4	O14682-1
ENC1	ENST00000618628.4 linkuse as main transcript	c.1560G>A	p.Lys520Lys	synonymous_variant	3/4	5		ENSP00000479101.1	O14682-1
ENC1	ENST00000651128.1 linkuse as main transcript	c.1560G>A	p.Lys520Lys	synonymous_variant	3/4			ENSP00000499185.1	O14682-1
ENC1	ENST00000510316.5 linkuse as main transcript	c.1341G>A	p.Lys447Lys	synonymous_variant	2/3	2		ENSP00000423804.1	O14682-2

Frequencies

GnomAD3 genomes

AF:

0.627

AC:

95312

AN:

151924

Hom.:

30103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.498

Gnomad AMR

AF:

0.728

Gnomad ASJ

AF:

0.729

Gnomad EAS

AF:

0.655

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.622

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.646

Gnomad OTH

AF:

0.666

GnomAD3 exomes

AF:

0.651

AC:

163700

AN:

251456

Hom.:

53980

AF XY:

0.647

AC XY:

87894

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.558

Gnomad AMR exome

AF:

0.766

Gnomad ASJ exome

AF:

0.732

Gnomad EAS exome

AF:

0.650

Gnomad SAS exome

AF:

0.569

Gnomad FIN exome

AF:

0.617

Gnomad NFE exome

AF:

0.650

Gnomad OTH exome

AF:

0.670

GnomAD4 exome

AF:

0.641

AC:

936283

AN:

1461496

Hom.:

301325

Cov.:

AF XY:

0.638

AC XY:

464195

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.556

Gnomad4 AMR exome

AF:

0.757

Gnomad4 ASJ exome

AF:

0.729

Gnomad4 EAS exome

AF:

0.662

Gnomad4 SAS exome

AF:

0.566

Gnomad4 FIN exome

AF:

0.621

Gnomad4 NFE exome

AF:

0.641

Gnomad4 OTH exome

AF:

0.648

GnomAD4 genome

AF:

0.627

AC:

95371

AN:

152042

Hom.:

30121

Cov.:

AF XY:

0.624

AC XY:

46398

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.557

Gnomad4 AMR

AF:

0.729

Gnomad4 ASJ

AF:

0.729

Gnomad4 EAS

AF:

0.654

Gnomad4 SAS

AF:

0.561

Gnomad4 FIN

AF:

0.622

Gnomad4 NFE

AF:

0.646

Gnomad4 OTH

AF:

0.664

Alfa

AF:

0.644

Hom.:

23374

Bravo

AF:

0.638

Asia WGS

AF:

0.608

AC:

2114

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.4

DANN

Benign

0.58

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over