Variant chr11-7509515-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198474.4(OLFML1):c.536T>C(p.Ile179Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OLFML1
NM_198474.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.202

Variant links:

Genes affected

OLFML1 (HGNC:24473): (olfactomedin like 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

OLFML1 links:

LOC124902806 (HGNC:):

LOC124902806 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035995215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFML1	NM_198474.4 linkuse as main transcript	c.536T>C	p.Ile179Thr	missense_variant	3/3	ENST00000329293.4	NP_940876.2	Q6UWY5Q5HYE3
OLFML1	NM_001370498.1 linkuse as main transcript	c.536T>C	p.Ile179Thr	missense_variant	4/4		NP_001357427.1
OLFML1	NM_001370499.1 linkuse as main transcript	c.128T>C	p.Ile43Thr	missense_variant	3/3		NP_001357428.1
LOC124902806	XM_047428005.1 linkuse as main transcript	c.*1088-1332A>G		intron_variant			XP_047283961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLFML1	ENST00000329293.4 linkuse as main transcript	c.536T>C	p.Ile179Thr	missense_variant	3/3	1	NM_198474.4	ENSP00000332511.3		Q6UWY5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251456

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.536T>C (p.I179T) alteration is located in exon 3 (coding exon 3) of the OLFML1 gene. This alteration results from a T to C substitution at nucleotide position 536, causing the isoleucine (I) at amino acid position 179 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.68

.;T

M_CAP

Benign

0.059

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.3

L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

1.7

N;N

REVEL

Benign

0.24

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0050

B;B

Vest4

0.086

MutPred

0.57

Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);

MVP

0.42

MPC

0.032

ClinPred

0.019

GERP RS

1.9

Varity_R

0.063

gMVP

0.22

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

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