5-74634926-C-T

Variant names:

• chr5-74634926-C-T
• rs300239
• NM_003633.4:c.1560G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.778
• Publications: 20 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ENC1	NM_003633.4	c.1560G>A	p.Lys520Lys	synonymous_variant	Exon 2 of 3	ENST00000302351.9	NP_003624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENC1	ENST00000302351.9	c.1560G>A	p.Lys520Lys	synonymous_variant	Exon 2 of 3	1	NM_003633.4	ENSP00000306356.4
ENC1	ENST00000618628.4	c.1560G>A	p.Lys520Lys	synonymous_variant	Exon 3 of 4	5		ENSP00000479101.1
ENC1	ENST00000651128.1	c.1560G>A	p.Lys520Lys	synonymous_variant	Exon 3 of 4			ENSP00000499185.1
ENC1	ENST00000510316.5	c.1341G>A	p.Lys447Lys	synonymous_variant	Exon 2 of 3	2		ENSP00000423804.1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95312 AN: 151924 Hom.: 30103 Cov.: 32

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

GnomAD2 exomes AF: 0.651 AC: 163700 AN: 251456 AF XY: 0.647

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 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.: 47 AF XY: 0.638 AC XY: 464195 AN XY: 727064

African (AFR) AF: 0.556 AC: 18624 AN: 33476

American (AMR) AF: 0.757 AC: 33853 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 19061 AN: 26134

East Asian (EAS) AF: 0.662 AC: 26279 AN: 39700

South Asian (SAS) AF: 0.566 AC: 48806 AN: 86254

European-Finnish (FIN) AF: 0.621 AC: 33159 AN: 53416

Middle Eastern (MID) AF: 0.747 AC: 4305 AN: 5766

European-Non Finnish (NFE) AF: 0.641 AC: 713036 AN: 1111638

Other (OTH) AF: 0.648 AC: 39160 AN: 60388

GnomAD4 genome AF: 0.627 AC: 95371 AN: 152042 Hom.: 30121 Cov.: 32 AF XY: 0.624 AC XY: 46398 AN XY: 74326

African (AFR) AF: 0.557 AC: 23093 AN: 41470

American (AMR) AF: 0.729 AC: 11136 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2531 AN: 3470

East Asian (EAS) AF: 0.654 AC: 3368 AN: 5148

South Asian (SAS) AF: 0.561 AC: 2702 AN: 4818

European-Finnish (FIN) AF: 0.622 AC: 6561 AN: 10556

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43899 AN: 67982

Other (OTH) AF: 0.664 AC: 1399 AN: 2108

Alfa AF: 0.644 Hom.: 31053

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
PhyloP100		0.78
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs300239; hg19: chr5-73930751; COSMIC: COSV56629725; COSMIC: COSV56629725;