rs12562197

Variant names:

• chr1-21245108-G-A
• rs12562197
• NM_001397.3:c.1164-5C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-21245108-G-A
• chr1-21245108-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001397.3(ECE1):​c.1164-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,612,490 control chromosomes in the GnomAD database, including 57,766 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4204 hom., cov: 32)
  • Exomes 𝑓: 0.27 (53562 hom.)
• Consequence: ECE1 NM_001397.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001958
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00100
• Publications: 14 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-21245108-G-A is Benign according to our data. Variant chr1-21245108-G-A is described in ClinVar as Benign. ClinVar VariationId is 258081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECE1	NM_001397.3	c.1164-5C>T		splice_region_variant, intron_variant	Intron 9 of 18	ENST00000374893.11	NP_001388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECE1	ENST00000374893.11	c.1164-5C>T		splice_region_variant, intron_variant	Intron 9 of 18	1	NM_001397.3	ENSP00000364028.6

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32097 AN: 152026 Hom.: 4207 Cov.: 32

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.222

GnomAD2 exomes AF: 0.236 AC: 59041 AN: 250150 AF XY: 0.240

Gnomad AFR exome AF: 0.0615

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.129

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.284

Gnomad OTH exome AF: 0.244

GnomAD4 exome AF: 0.266 AC: 387964 AN: 1460346 Hom.: 53562 Cov.: 33 AF XY: 0.264 AC XY: 191880 AN XY: 726528

African (AFR) AF: 0.0584 AC: 1952 AN: 33452

American (AMR) AF: 0.217 AC: 9702 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 5457 AN: 26124

East Asian (EAS) AF: 0.139 AC: 5515 AN: 39682

South Asian (SAS) AF: 0.205 AC: 17684 AN: 86202

European-Finnish (FIN) AF: 0.298 AC: 15887 AN: 53324

Middle Eastern (MID) AF: 0.240 AC: 1377 AN: 5744

European-Non Finnish (NFE) AF: 0.284 AC: 315868 AN: 1110876

Other (OTH) AF: 0.241 AC: 14522 AN: 60326

GnomAD4 genome AF: 0.211 AC: 32100 AN: 152144 Hom.: 4204 Cov.: 32 AF XY: 0.209 AC XY: 15582 AN XY: 74390

African (AFR) AF: 0.0637 AC: 2645 AN: 41550

American (AMR) AF: 0.247 AC: 3767 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 686 AN: 3464

East Asian (EAS) AF: 0.131 AC: 677 AN: 5172

South Asian (SAS) AF: 0.190 AC: 915 AN: 4828

European-Finnish (FIN) AF: 0.310 AC: 3283 AN: 10596

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19371 AN: 67962

Other (OTH) AF: 0.219 AC: 461 AN: 2106

Alfa AF: 0.253 Hom.: 19014

Bravo AF: 0.199

Asia WGS AF: 0.154 AC: 539 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.67
PhyloP100		-0.0010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0
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: rs12562197; hg19: chr1-21571601; COSMIC: COSV51662497;