9-135077048-GA-G

Position:

• chr9-135077048-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000371799.8(OLFM1):​c.334del​(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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.731

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 -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFM1	NM_006334.4	c.96+1247del		intron_variant			NP_006325.1
OLFM1	NM_014279.5	c.96+1247del		intron_variant			NP_055094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLFM1	ENST00000371799.8	c.334del	p.Arg112GlyfsTer58	frameshift_variant	2/2	1		ENSP00000360864
OLFM1	ENST00000252854.8	c.96+1247del		intron_variant		1		ENSP00000252854
OLFM1	ENST00000277415.15	c.96+1247del		intron_variant		1		ENSP00000277415

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1225 AN: 117930 Hom.: 20 Cov.: 32

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

GnomAD4 exome AF: 0.00320 AC: 4473 AN: 1398266 Hom.: 98 Cov.: 30 AF XY: 0.00400 AC XY: 2760 AN XY: 689646

Gnomad4 AFR exome AF: 0.0229

Gnomad4 AMR exome AF: 0.000980

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0272

Gnomad4 SAS exome AF: 0.0294

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000117

Gnomad4 OTH exome AF: 0.00464

GnomAD4 genome AF: 0.0105 AC: 1234 AN: 118050 Hom.: 21 Cov.: 32 AF XY: 0.0112 AC XY: 627 AN XY: 56220

Gnomad4 AFR AF: 0.0309

Gnomad4 AMR AF: 0.00420

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0240

Gnomad4 SAS AF: 0.0503

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000868

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.000229 Hom.: 0

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

OLFM1: BS1, BS2 -

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: rs3841031; hg19: chr9-137968894;