NM_001397.3:c.1671-21_1671-20delCTinsGG

Variant names:

• chr1-21228061-AG-CC
• rs886038483
• NM_001397.3:c.1671-21_1671-20delCTinsGG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001397.3(ECE1):​c.1671-21_1671-20delCTinsGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ECE1 NM_001397.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.764
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• essential hypertension, genetic

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 1-21228061-AG-CC is Benign according to our data. Variant chr1-21228061-AG-CC is described in ClinVar as Likely_benign. ClinVar VariationId is 258086.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001397.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECE1	NM_001397.3	MANE Select	c.1671-21_1671-20delCTinsGG		intron	N/A	NP_001388.1	P42892-1
	ECE1	NM_001113349.2		c.1662-21_1662-20delCTinsGG		intron	N/A	NP_001106820.1	P42892-4
	ECE1	NM_001113347.2		c.1635-21_1635-20delCTinsGG		intron	N/A	NP_001106818.1	P42892-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECE1	ENST00000374893.11	TSL:1 MANE Select	c.1671-21_1671-20delCTinsGG		intron	N/A	ENSP00000364028.6	P42892-1
	ECE1	ENST00000264205.10	TSL:1	c.1662-21_1662-20delCTinsGG		intron	N/A	ENSP00000264205.6	P42892-4
	ECE1	ENST00000357071.8	TSL:1	c.1635-21_1635-20delCTinsGG		intron	N/A	ENSP00000349581.4	P42892-2

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs886038483; hg19: chr1-21554554;