chr9-135119662-G-A

Variant names:

• chr9-135119662-G-A
• rs115071335
• NM_001282611.2:c.942G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001282611.2(OLFM1):​c.942G>A​(p.Lys314Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,614,164 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00056 (5 hom.)
• Consequence: OLFM1 NM_001282611.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.39
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 9-135119662-G-A is Benign according to our data. Variant chr9-135119662-G-A is described in ClinVar as Benign. ClinVar VariationId is 787891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.39 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00536 (816/152320) while in subpopulation AFR AF = 0.0189 (786/41556). AF 95% confidence interval is 0.0178. There are 7 homozygotes in GnomAd4. There are 380 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282611.2. 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_001282611.2	MANE Select	c.942G>A	p.Lys314Lys	synonymous	Exon 6 of 6	NP_001269540.1	Q99784-1
	OLFM1	NM_001282612.1		c.861G>A	p.Lys287Lys	synonymous	Exon 6 of 6	NP_001269541.1	Q99784-5
	OLFM1	NM_014279.7		c.858G>A	p.Lys286Lys	synonymous	Exon 6 of 6	NP_055094.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFM1	ENST00000371793.8	TSL:3 MANE Select	c.942G>A	p.Lys314Lys	synonymous	Exon 6 of 6	ENSP00000360858.3	Q99784-1
	OLFM1	ENST00000252854.8	TSL:1	c.888G>A	p.Lys296Lys	synonymous	Exon 6 of 6	ENSP00000252854.4	Q99784-3
	OLFM1	ENST00000483042.1	TSL:1	n.1375G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00534 AC: 813 AN: 152202 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00153 AC: 385 AN: 251444 AF XY: 0.00128

Gnomad AFR exome AF: 0.0206

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000560 AC: 818 AN: 1461844 Hom.: 5 Cov.: 32 AF XY: 0.000494 AC XY: 359 AN XY: 727214

African (AFR) AF: 0.0199 AC: 666 AN: 33480

American (AMR) AF: 0.00148 AC: 66 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1112008

Other (OTH) AF: 0.00118 AC: 71 AN: 60394

GnomAD4 genome AF: 0.00536 AC: 816 AN: 152320 Hom.: 7 Cov.: 33 AF XY: 0.00510 AC XY: 380 AN XY: 74482

African (AFR) AF: 0.0189 AC: 786 AN: 41556

American (AMR) AF: 0.00124 AC: 19 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00249 Hom.: 2

Bravo AF: 0.00586

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.62
PhyloP100		3.4
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs115071335; hg19: chr9-138011508;