Genetic Variant OLFM1:p.Thr151MetfsTer41 (chr9-135077150-GCA-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000371799.8(OLFM1):c.452_453delCA(p.Thr151MetfsTer41) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,390,134 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 0 hom. )

Consequence

OLFM1
ENST00000371799.8 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.399

Publications

4 publications found

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: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 9-135077150-GCA-G is Benign according to our data. Variant chr9-135077150-GCA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2673203.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371799.8. 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
	OLFM1	NM_014279.7		c.66+1365_66+1366delCA		intron	N/A	NP_055094.2
	OLFM1	NM_006334.6		c.66+1365_66+1366delCA		intron	N/A	NP_006325.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OLFM1	ENST00000371799.8	TSL:1	c.452_453delCA	p.Thr151MetfsTer41	frameshift	Exon 2 of 2	ENSP00000360864.4	Q6IMJ6
OLFM1	ENST00000252854.8	TSL:1	c.96+1365_96+1366delCA		intron	N/A	ENSP00000252854.4	Q99784-3
OLFM1	ENST00000277415.15	TSL:1	c.96+1365_96+1366delCA		intron	N/A	ENSP00000277415.11	Q99784-4

Frequencies

GnomAD3 genomes

AF:

0.000126

AC:

AN:

151076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000777

Gnomad SAS

AF:

0.000629

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0130

AC:

1438

AN:

110262

AF XY:

0.0142

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.00997

Gnomad ASJ exome

AF:

0.0199

Gnomad EAS exome

AF:

0.00473

Gnomad FIN exome

AF:

0.0101

Gnomad NFE exome

AF:

0.0153

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.00183

AC:

2264

AN:

1238952

Hom.:

AF XY:

0.00216

AC XY:

1313

AN XY:

609238

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000935

AC:

AN:

28890

American (AMR)

AF:

0.00691

AC:

210

AN:

30404

Ashkenazi Jewish (ASJ)

AF:

0.00515

AC:

109

AN:

21170

East Asian (EAS)

AF:

0.00282

AC:

AN:

28416

South Asian (SAS)

AF:

0.00709

AC:

475

AN:

67008

European-Finnish (FIN)

AF:

0.00345

AC:

138

AN:

40056

Middle Eastern (MID)

AF:

0.00258

AC:

AN:

5030

European-Non Finnish (NFE)

AF:

0.00116

AC:

1122

AN:

967658

Other (OTH)

AF:

0.00179

AC:

AN:

50320

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.264

Heterozygous variant carriers

334

668

1002

1336

1670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000126

AC:

AN:

151182

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

73842

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41246

American (AMR)

AF:

0.00

AC:

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.000779

AC:

AN:

5136

South Asian (SAS)

AF:

0.000629

AC:

AN:

4766

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10422

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67672

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0159

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.40

Mutation Taster

=149/51

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over