NM_001282611.2:c.717C>T

Variant names:

• chr9-135106789-C-T
• rs78249091
• NM_001282611.2:c.717C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001282611.2(OLFM1):​c.717C>T​(p.Val239Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,613,690 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (77 hom., cov: 34)
  • Exomes 𝑓: 0.0024 (95 hom.)
• Consequence: OLFM1 NM_001282611.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.16
• Publications: 3 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 9-135106789-C-T is Benign according to our data. Variant chr9-135106789-C-T is described in ClinVar as Benign. ClinVar VariationId is 768338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

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.717C>T	p.Val239Val	synonymous	Exon 5 of 6	NP_001269540.1	Q99784-1
	OLFM1	NM_001282612.1		c.636C>T	p.Val212Val	synonymous	Exon 5 of 6	NP_001269541.1	Q99784-5
	OLFM1	NM_014279.7		c.633C>T	p.Val211Val	synonymous	Exon 5 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.717C>T	p.Val239Val	synonymous	Exon 5 of 6	ENSP00000360858.3	Q99784-1
	OLFM1	ENST00000252854.8	TSL:1	c.663C>T	p.Val221Val	synonymous	Exon 5 of 6	ENSP00000252854.4	Q99784-3
	OLFM1	ENST00000483042.1	TSL:1	n.1150C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3037 AN: 152218 Hom.: 77 Cov.: 34

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00798

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00563 AC: 1407 AN: 249878 AF XY: 0.00421

Gnomad AFR exome AF: 0.0692

Gnomad AMR exome AF: 0.00597

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000497

Gnomad OTH exome AF: 0.00443

GnomAD4 exome AF: 0.00239 AC: 3490 AN: 1461354 Hom.: 95 Cov.: 30 AF XY: 0.00214 AC XY: 1554 AN XY: 726932

African (AFR) AF: 0.0711 AC: 2379 AN: 33472

American (AMR) AF: 0.00622 AC: 278 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53164

Middle Eastern (MID) AF: 0.00572 AC: 33 AN: 5768

European-Non Finnish (NFE) AF: 0.000409 AC: 455 AN: 1111884

Other (OTH) AF: 0.00543 AC: 328 AN: 60368

GnomAD4 genome AF: 0.0200 AC: 3047 AN: 152336 Hom.: 77 Cov.: 34 AF XY: 0.0193 AC XY: 1435 AN XY: 74498

African (AFR) AF: 0.0689 AC: 2865 AN: 41570

American (AMR) AF: 0.00797 AC: 122 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68024

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.0105 Hom.: 32

Bravo AF: 0.0234

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000593

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	-0.29
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs78249091; hg19: chr9-137998635;