rs3914188

Variant names:

• chr3-184292260-G-C
• rs3914188
• NM_001100121.2:c.*22G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100121.2(ECE2):​c.*22G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,611,682 control chromosomes in the GnomAD database, including 432,121 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 0.73 (40981 hom., cov: 33)
  • Exomes 𝑓: 0.73 (391140 hom.)
• Consequence: ECE2 NM_001100121.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• Publications: 36 publications found

Genes affected

ECE2 (HGNC:13275): (endothelin converting enzyme 2) Enables metalloendopeptidase activity. Involved in peptide hormone processing. Located in cytoplasmic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

EEF1AKMT4-ECE2 (HGNC:53615): (EEF1AKMT4-ECE2 readthrough) This gene represents naturally occurring readthrough transcription between adjacent genes eukaryotic translation elongation factor 1 alpha lysine methyltransferase 4 (GeneID: 110599564) and endothelin converting enzyme 2 (GeneID:9718). The readthrough transcript representing this gene encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECE2	NM_001100121.2	c.*22G>C		3_prime_UTR_variant	Exon 19 of 19	ENST00000404464.8	NP_001093591.1
EEF1AKMT4-ECE2	NM_014693.4	c.*22G>C		3_prime_UTR_variant	Exon 19 of 19		NP_055508.3
ECE2	NM_001100120.2	c.*22G>C		3_prime_UTR_variant	Exon 19 of 19		NP_001093590.1
ECE2	NM_001037324.3	c.*22G>C		3_prime_UTR_variant	Exon 18 of 18		NP_001032401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECE2	ENST00000404464.8	c.*22G>C		3_prime_UTR_variant	Exon 19 of 19	1	NM_001100121.2	ENSP00000385846.3
EEF1AKMT4-ECE2	ENST00000402825.7	c.*22G>C		3_prime_UTR_variant	Exon 19 of 19	1		ENSP00000384223.3

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111366 AN: 152022 Hom.: 40957 Cov.: 33

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.769

GnomAD2 exomes AF: 0.734 AC: 182827 AN: 249142 AF XY: 0.730

Gnomad AFR exome AF: 0.736

Gnomad AMR exome AF: 0.816

Gnomad ASJ exome AF: 0.835

Gnomad EAS exome AF: 0.634

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.739

Gnomad OTH exome AF: 0.749

GnomAD4 exome AF: 0.731 AC: 1067083 AN: 1459544 Hom.: 391140 Cov.: 47 AF XY: 0.730 AC XY: 529529 AN XY: 725820

African (AFR) AF: 0.734 AC: 24550 AN: 33432

American (AMR) AF: 0.812 AC: 36222 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 21798 AN: 26078

East Asian (EAS) AF: 0.629 AC: 24932 AN: 39656

South Asian (SAS) AF: 0.685 AC: 59081 AN: 86188

European-Finnish (FIN) AF: 0.675 AC: 35863 AN: 53164

Middle Eastern (MID) AF: 0.835 AC: 4809 AN: 5760

European-Non Finnish (NFE) AF: 0.734 AC: 815021 AN: 1110364

Other (OTH) AF: 0.743 AC: 44807 AN: 60272

GnomAD4 genome AF: 0.732 AC: 111436 AN: 152138 Hom.: 40981 Cov.: 33 AF XY: 0.727 AC XY: 54104 AN XY: 74390

African (AFR) AF: 0.740 AC: 30719 AN: 41512

American (AMR) AF: 0.787 AC: 12045 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2889 AN: 3472

East Asian (EAS) AF: 0.623 AC: 3217 AN: 5162

South Asian (SAS) AF: 0.675 AC: 3253 AN: 4822

European-Finnish (FIN) AF: 0.666 AC: 7055 AN: 10596

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.733 AC: 49798 AN: 67958

Other (OTH) AF: 0.760 AC: 1609 AN: 2116

Alfa AF: 0.757 Hom.: 6741

Bravo AF: 0.746

Asia WGS AF: 0.653 AC: 2275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.7
DANN	Benign	0.64
PhyloP100		1.7
Mutation Taster		=100/0	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: rs3914188; hg19: chr3-184010048; COSMIC: COSV62569017; COSMIC: COSV62569017;