1-113981133-C-A

Variant names:

• chr1-113981133-C-A
• rs1270279548
• NM_020190.5:c.585C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_020190.5(OLFML3):​c.585C>A​(p.Ala195Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OLFML3 NM_020190.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.691
• Publications: 0 publications found

Genes affected

OLFML3 (HGNC:24956): (olfactomedin like 3) This gene encodes a member of the olfactomedin-like gene family which also includes genes encoding noelin, tiarin, myocilin, amassin, optimedin, photomedin, and latrophilin. The encoded protein is a secreted extracellular matrix glycoprotein with a C-terminal olfactomedin domain that facilitates protein-protein interactions, cell adhesion, and intercellular interactions. It serves as both a scaffold protein that recruits bone morphogenetic protein 1 to its substrate chordin, and as a vascular tissue remodeler with pro-angiogenic properties. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 1-113981133-C-A is Benign according to our data. Variant chr1-113981133-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2681450.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.691 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020190.5. 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
	OLFML3	NM_020190.5	MANE Select	c.585C>A	p.Ala195Ala	synonymous	Exon 3 of 3	NP_064575.1	M1LAK4
	OLFML3	NM_001286352.3		c.525C>A	p.Ala175Ala	synonymous	Exon 4 of 4	NP_001273281.1	Q9NRN5-2
	OLFML3	NM_001286353.3		c.402C>A	p.Ala134Ala	synonymous	Exon 3 of 3	NP_001273282.1	B4DNG0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFML3	ENST00000320334.5	TSL:1 MANE Select	c.585C>A	p.Ala195Ala	synonymous	Exon 3 of 3	ENSP00000322273.4	Q9NRN5-1
	OLFML3	ENST00000854415.1		c.585C>A	p.Ala195Ala	synonymous	Exon 4 of 4	ENSP00000524474.1
	OLFML3	ENST00000933255.1		c.561C>A	p.Ala187Ala	synonymous	Exon 3 of 3	ENSP00000603314.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	EBV-positive nodal T- and NK-cell lymphoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	10
DANN	Benign	0.83
PhyloP100		0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1270279548; hg19: chr1-114523755;