Variant 19-9854869-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_058164.4(OLFM2):c.688-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,566,102 control chromosomes in the GnomAD database, including 110 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 0.015 ( 56 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 54 hom. )

Consequence

OLFM2
NM_058164.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006201

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.262

Variant links:

Genes affected

OLFM2 (HGNC:17189): (olfactomedin 2) Involved in positive regulation of smooth muscle cell differentiation. Acts upstream of or within protein secretion. Located in cytoplasm; extracellular region; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

OLFM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 19-9854869-G-A is Benign according to our data. Variant chr19-9854869-G-A is described in ClinVar as [Benign]. Clinvar id is 780531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
OLFM2	NM_058164.4 linkuse as main transcript	c.688-6C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000264833.9
OLFM2	NM_001304347.2 linkuse as main transcript	c.760-6C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
OLFM2	NM_001304348.2 linkuse as main transcript	c.454-6C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
OLFM2	XM_047439713.1 linkuse as main transcript	c.484-6C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
OLFM2	ENST00000264833.9 linkuse as main transcript	c.688-6C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_058164.4
OLFM2	ENST00000590841.5 linkuse as main transcript	c.454-6C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2
OLFM2	ENST00000593091.2 linkuse as main transcript	c.760-6C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5		P1
OLFM2	ENST00000592448.1 linkuse as main transcript	c.*93-6C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2299

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0526

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00383

AC:

735

AN:

191716

Hom.:

AF XY:

0.00297

AC XY:

310

AN XY:

104318

show subpopulations

Gnomad AFR exome

AF:

0.0556

Gnomad AMR exome

AF:

0.00244

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000424

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000830

Gnomad OTH exome

AF:

0.00232

GnomAD4 exome

AF:

0.00151

AC:

2140

AN:

1413852

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

897

AN XY:

698192

show subpopulations

Gnomad4 AFR exome

AF:

0.0553

Gnomad4 AMR exome

AF:

0.00260

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000304

Gnomad4 OTH exome

AF:

0.00328

GnomAD4 genome

AF:

0.0151

AC:

2301

AN:

152250

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1089

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0525

Gnomad4 AMR

AF:

0.00575

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00870

Hom.:

Bravo

AF:

0.0172

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.67

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000062

dbscSNV1_RF

Benign

0.0040

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