2-189783978-G-C

Variant names:

• chr2-189783978-G-C
• rs5742924
• NM_016467.5:c.-118+291C>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001371388.1(ORMDL1):​c.-107C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 152,352 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (155 hom., cov: 33)
  • Exomes 𝑓: 0.025 (0 hom.)
• Consequence: ORMDL1 NM_001371388.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.827

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-189783978-G-C is Benign according to our data. Variant chr2-189783978-G-C is described in ClinVar as [Benign]. Clinvar id is 1248274.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORMDL1	NM_016467.5	c.-118+291C>G		intron_variant	Intron 1 of 4	ENST00000392349.9	NP_057551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORMDL1	ENST00000392349.9	c.-118+291C>G		intron_variant	Intron 1 of 4	1	NM_016467.5	ENSP00000376160.4

Frequencies

GnomAD3 genomes AF: 0.0377 AC: 5736 AN: 152154 Hom.: 157 Cov.: 33

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.0280

Gnomad SAS AF: 0.0524

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0450

GnomAD4 exome AF: 0.0250 AC: 2 AN: 80 Hom.: 0 AF XY: 0.0303 AC XY: 2 AN XY: 66

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0147

GnomAD4 genome AF: 0.0377 AC: 5734 AN: 152272 Hom.: 155 Cov.: 33 AF XY: 0.0391 AC XY: 2908 AN XY: 74442

Gnomad4 AFR AF: 0.0668

Gnomad4 AMR AF: 0.0268

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.0279

Gnomad4 SAS AF: 0.0512

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.0441

Alfa AF: 0.0269 Hom.: 13

Bravo AF: 0.0371

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.3
DANN	Benign	0.38

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: rs5742924; hg19: chr2-190648704;