9-135077150-GCACA-GCACACA

Variant names:

• chr9-135077150-G-GCA
• rs147807021
• ENST00000371799.8:c.452_453dupCA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000371799.8(OLFM1):​c.452_453dupCA​(p.Cys152HisfsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 1,507,044 control chromosomes in the GnomAD database, including 984 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.063 (599 hom., cov: 32)
  • Exomes 𝑓: 0.022 (385 hom.)
• Consequence: OLFM1 ENST00000371799.8 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OLFM1	NM_014279.5	c.96+1365_96+1366dupCA		intron_variant	Intron 1 of 5		NP_055094.1
OLFM1	NM_006334.4	c.96+1365_96+1366dupCA		intron_variant	Intron 1 of 3		NP_006325.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLFM1	ENST00000371799.8	c.452_453dupCA	p.Cys152HisfsTer19	frameshift_variant	Exon 2 of 2	1		ENSP00000360864.4
OLFM1	ENST00000252854.8	c.96+1365_96+1366dupCA		intron_variant	Intron 1 of 5	1		ENSP00000252854.4
OLFM1	ENST00000277415.15	c.96+1365_96+1366dupCA		intron_variant	Intron 1 of 3	1		ENSP00000277415.11

Frequencies

GnomAD3 genomes AF: 0.0629 AC: 9504 AN: 151138 Hom.: 597 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0229

Gnomad EAS AF: 0.00175

Gnomad SAS AF: 0.0111

Gnomad FIN AF: 0.0526

Gnomad MID AF: 0.0290

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0541

GnomAD3 exomes AF: 0.0332 AC: 3659 AN: 110262 Hom.: 16 AF XY: 0.0303 AC XY: 1764 AN XY: 58244

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.0283

Gnomad ASJ exome AF: 0.0348

Gnomad EAS exome AF: 0.00231

Gnomad SAS exome AF: 0.0118

Gnomad FIN exome AF: 0.0558

Gnomad NFE exome AF: 0.0237

Gnomad OTH exome AF: 0.0385

GnomAD4 exome AF: 0.0216 AC: 29321 AN: 1355800 Hom.: 385 Cov.: 34 AF XY: 0.0207 AC XY: 13844 AN XY: 667994

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.0252

Gnomad4 ASJ exome AF: 0.0236

Gnomad4 EAS exome AF: 0.00673

Gnomad4 SAS exome AF: 0.00896

Gnomad4 FIN exome AF: 0.0341

Gnomad4 NFE exome AF: 0.0176

Gnomad4 OTH exome AF: 0.0276

GnomAD4 genome AF: 0.0630 AC: 9521 AN: 151244 Hom.: 599 Cov.: 32 AF XY: 0.0632 AC XY: 4668 AN XY: 73884

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.0346

Gnomad4 ASJ AF: 0.0229

Gnomad4 EAS AF: 0.00175

Gnomad4 SAS AF: 0.0109

Gnomad4 FIN AF: 0.0526

Gnomad4 NFE AF: 0.0171

Gnomad4 OTH AF: 0.0535

Bravo AF: 0.0663

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs147807021; hg19: chr9-137968996;