Variant 2-189784079-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_016467.5(ORMDL1):c.-118+190C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,424 control chromosomes in the GnomAD database, including 1,183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1181 hom., cov: 33)

Exomes 𝑓: 0.22 ( 2 hom. )

Consequence

ORMDL1
NM_016467.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.156

Variant links:

Genes affected

ORMDL1 (HGNC:16036): (ORMDL sphingolipid biosynthesis regulator 1) Involved in ceramide metabolic process. Acts upstream of or within negative regulation of ceramide biosynthetic process. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ORMDL1 links:

ORMDL1 (HGNC:):

ORMDL1 links:

PMS1 (HGNC:9121): (PMS1 homolog 1, mismatch repair system component) This gene encodes a protein belonging to the DNA mismatch repair mutL/hexB family. This protein is thought to be involved in the repair of DNA mismatches, and it can form heterodimers with MLH1, a known DNA mismatch repair protein. Mutations in this gene cause hereditary nonpolyposis colorectal cancer type 3 (HNPCC3) either alone or in combination with mutations in other genes involved in the HNPCC phenotype, which is also known as Lynch syndrome. [provided by RefSeq, Jul 2008]

PMS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-189784079-G-T is Benign according to our data. Variant chr2-189784079-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 369322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORMDL1	NM_016467.5 linkuse as main transcript	c.-118+190C>A		intron_variant		ENST00000392349.9	NP_057551.1	Q9P0S3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORMDL1	ENST00000392349.9 linkuse as main transcript	c.-118+190C>A		intron_variant		1	NM_016467.5	ENSP00000376160.4		Q9P0S3

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17355

AN:

152116

Hom.:

1180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0546

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.0910

Gnomad SAS

AF:

0.0795

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.124

GnomAD4 exome

AF:

0.223

AC:

AN:

188

Hom.:

Cov.:

AF XY:

0.216

AC XY:

AN XY:

134

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.247

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.114

AC:

17357

AN:

152236

Hom.:

1181

Cov.:

AF XY:

0.112

AC XY:

8349

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0546

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.189

Gnomad4 EAS

AF:

0.0910

Gnomad4 SAS

AF:

0.0789

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.142

Hom.:

1530

Bravo

AF:

0.111

Asia WGS

AF:

0.109

AC:

378

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Lynch syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

This variant is associated with the following publications: (PMID: 24710284) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.6

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.34

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.34

Position offset: 3

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over