1-21219863-G-T

Position:

• chr1-21219863-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001397.3(ECE1):​c.*92C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,549,356 control chromosomes in the GnomAD database, including 802 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 0.023 (76 hom., cov: 32)
  • Exomes 𝑓: 0.030 (726 hom.)
• Consequence: ECE1 NM_001397.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236

Genes affected

ECE1 (HGNC:3146): (endothelin converting enzyme 1) The protein encoded by this gene is involved in proteolytic processing of endothelin precursors to biologically active peptides. Mutations in this gene are associated with Hirschsprung disease, cardiac defects and autonomic dysfunction. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Sep 2009]

ECE1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0234 (3565/152344) while in subpopulation NFE AF= 0.031 (2106/68022). AF 95% confidence interval is 0.0299. There are 76 homozygotes in gnomad4. There are 1822 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3565 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECE1	NM_001397.3	c.*92C>A		3_prime_UTR_variant	19/19	ENST00000374893.11	NP_001388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECE1	ENST00000374893.11	c.*92C>A		3_prime_UTR_variant	19/19	1	NM_001397.3	ENSP00000364028.6

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3569 AN: 152226 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.00613

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0174

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00682

Gnomad FIN AF: 0.0657

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0310

Gnomad OTH AF: 0.0220

GnomAD4 exome AF: 0.0298 AC: 41626 AN: 1397012 Hom.: 726 Cov.: 26 AF XY: 0.0292 AC XY: 20289 AN XY: 694334

Gnomad4 AFR exome AF: 0.00368

Gnomad4 AMR exome AF: 0.0115

Gnomad4 ASJ exome AF: 0.0333

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00819

Gnomad4 FIN exome AF: 0.0620

Gnomad4 NFE exome AF: 0.0326

Gnomad4 OTH exome AF: 0.0267

GnomAD4 genome AF: 0.0234 AC: 3565 AN: 152344 Hom.: 76 Cov.: 32 AF XY: 0.0245 AC XY: 1822 AN XY: 74500

Gnomad4 AFR AF: 0.00611

Gnomad4 AMR AF: 0.0174

Gnomad4 ASJ AF: 0.0375

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00683

Gnomad4 FIN AF: 0.0657

Gnomad4 NFE AF: 0.0310

Gnomad4 OTH AF: 0.0217

Alfa AF: 0.0287 Hom.: 19

Bravo AF: 0.0197

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.6
DANN	Benign	0.78
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

Other links and lift over

dbSNP: rs3026907; hg19: chr1-21546356;