chr3-184278307-T-C

Position:

• chr3-184278307-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001100121.2(ECE2):​c.744T>C​(p.Val248Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,613,942 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (27 hom.)
• Consequence: ECE2 NM_001100121.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.10

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]

ECE2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 3-184278307-T-C is Benign according to our data. Variant chr3-184278307-T-C is described in ClinVar as [Benign]. Clinvar id is 780899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1628/152234) while in subpopulation AFR AF= 0.0379 (1575/41520). AF 95% confidence interval is 0.0364. There are 27 homozygotes in gnomad4. There are 743 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECE2	NM_001100121.2	c.744T>C	p.Val248Val	synonymous_variant	6/19	ENST00000404464.8	NP_001093591.1
EEF1AKMT4-ECE2	NM_014693.4	c.1098T>C	p.Val366Val	synonymous_variant	6/19		NP_055508.3
ECE2	NM_001100120.2	c.882T>C	p.Val294Val	synonymous_variant	6/19		NP_001093590.1
ECE2	NM_001037324.3	c.657T>C	p.Val219Val	synonymous_variant	5/18		NP_001032401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECE2	ENST00000404464.8	c.744T>C	p.Val248Val	synonymous_variant	6/19	1	NM_001100121.2	ENSP00000385846.3
EEF1AKMT4-ECE2	ENST00000402825.7	c.1098T>C	p.Val366Val	synonymous_variant	6/19	1		ENSP00000384223.3

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1623 AN: 152116 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00264 AC: 662 AN: 250730 Hom.: 15 AF XY: 0.00179 AC XY: 243 AN XY: 135464

Gnomad AFR exome AF: 0.0378

Gnomad AMR exome AF: 0.000956

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000982

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000618

Gnomad OTH exome AF: 0.000817

GnomAD4 exome AF: 0.00111 AC: 1628 AN: 1461708 Hom.: 27 Cov.: 36 AF XY: 0.000961 AC XY: 699 AN XY: 727140

Gnomad4 AFR exome AF: 0.0413

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00227

GnomAD4 genome AF: 0.0107 AC: 1628 AN: 152234 Hom.: 27 Cov.: 32 AF XY: 0.00998 AC XY: 743 AN XY: 74430

Gnomad4 AFR AF: 0.0379

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00562 Hom.: 8

Bravo AF: 0.0115

EpiCase AF: 0.0000545

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.8
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs76939864; hg19: chr3-183996095;