Genetic Variant OLFM1:p.Arg112GlyfsTer58 (chr9-135077048-GA-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000371799.8(OLFM1):c.334delA(p.Arg112GlyfsTer58) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 1,516,316 control chromosomes in the GnomAD database, including 119 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 21 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 98 hom. )

Consequence

OLFM1
ENST00000371799.8 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.731

Variant links:

Genes affected

OLFM1 (HGNC:17187): (olfactomedin 1) This gene product shares extensive sequence similarity with the rat neuronal olfactomedin-related ER localized protein. While the exact function of the encoded protein is not known, its abundant expression in brain suggests that it may have an essential role in nerve tissue. Several alternatively spliced transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OLFM1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 9-135077048-GA-G is Benign according to our data. Variant chr9-135077048-GA-G is described in ClinVar as [Benign]. Clinvar id is 2659707.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0105 (1234/118050) while in subpopulation SAS AF = 0.0503 (158/3144). AF 95% confidence interval is 0.0439. There are 21 homozygotes in GnomAd4. There are 627 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OLFM1	NM_014279.5 link	c.96+1247delA		intron_variant	Intron 1 of 5		NP_055094.1	Q99784-3Q6IMJ8
OLFM1	NM_006334.4 link	c.96+1247delA		intron_variant	Intron 1 of 3		NP_006325.1	Q99784-4Q6IMJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
OLFM1	ENST00000371799.8 link	c.334delA	p.Arg112GlyfsTer58	frameshift_variant	Exon 2 of 2	1	ENSP00000360864.4	Q6IMJ6
OLFM1	ENST00000252854.8 link	c.96+1247delA		intron_variant	Intron 1 of 5	1	ENSP00000252854.4	Q99784-3
OLFM1	ENST00000277415.15 link	c.96+1247delA		intron_variant	Intron 1 of 3	1	ENSP00000277415.11	Q99784-4

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1225

AN:

117930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00421

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0239

Gnomad SAS

AF:

0.0502

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000868

Gnomad OTH

AF:

0.00680

GnomAD2 exomes

AF:

0.00448

AC:

654

AN:

146030

AF XY:

0.00572

show subpopulations

Gnomad AFR exome

AF:

0.0107

Gnomad AMR exome

AF:

0.000575

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00674

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000166

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00320

AC:

4473

AN:

1398266

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

2760

AN XY:

689646

show subpopulations

Gnomad4 AFR exome

AF:

0.0229

AC:

724

AN:

31594

Gnomad4 AMR exome

AF:

0.000980

AC:

AN:

35702

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25174

Gnomad4 EAS exome

AF:

0.0272

AC:

973

AN:

35738

Gnomad4 SAS exome

AF:

0.0294

AC:

2333

AN:

79230

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

48168

Gnomad4 NFE exome

AF:

0.000117

AC:

126

AN:

1078968

Gnomad4 Remaining exome

AF:

0.00464

AC:

269

AN:

57994

Heterozygous variant carriers

287

574

861

1148

1435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0105

AC:

1234

AN:

118050

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

627

AN XY:

56220

show subpopulations

Gnomad4 AFR

AF:

0.0309

AC:

0.0309368

AN:

0.0309368

Gnomad4 AMR

AF:

0.00420

AC:

0.00420409

AN:

0.00420409

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.0240

AC:

0.0239536

AN:

0.0239536

Gnomad4 SAS

AF:

0.0503

AC:

0.0502545

AN:

0.0502545

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000868

AC:

0.0000868086

AN:

0.0000868086

Gnomad4 OTH

AF:

0.00803

AC:

0.00803213

AN:

0.00803213

Heterozygous variant carriers

118

178

237

296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000229

Hom.:

Bravo

AF:

0.00836

Asia WGS

AF:

0.0300

AC:

104

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

OLFM1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=149/51

polymorphism

Splicing

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