NM_058164.4:c.317G>A

Variant names:

• chr19-9857758-C-T
• rs2303100
• NM_058164.4:c.317G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_058164.4(OLFM2):​c.317G>A​(p.Arg106Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,613,768 control chromosomes in the GnomAD database, including 217,891 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (15418 hom., cov: 32)
  • Exomes 𝑓: 0.52 (202473 hom.)
• Consequence: OLFM2 NM_058164.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.625
• Publications: 29 publications found

Genes affected

OLFM2 (HGNC:17189): (olfactomedin 2) Involved in positive regulation of smooth muscle cell differentiation. Acts upstream of or within protein secretion. Located in cytoplasm; extracellular region; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.5246563E-4).
• BP6: Variant 19-9857758-C-T is Benign according to our data. Variant chr19-9857758-C-T is described in ClinVar as Benign. ClinVar VariationId is 1297260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058164.4. 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
	OLFM2	NM_058164.4	MANE Select	c.317G>A	p.Arg106Gln	missense	Exon 3 of 6	NP_477512.1	O95897
	OLFM2	NM_001304347.2		c.389G>A	p.Arg130Gln	missense	Exon 3 of 6	NP_001291276.1	K7EKW2
	OLFM2	NM_001304348.2		c.83G>A	p.Arg28Gln	missense	Exon 2 of 5	NP_001291277.1	K7EIS8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFM2	ENST00000264833.9	TSL:1 MANE Select	c.317G>A	p.Arg106Gln	missense	Exon 3 of 6	ENSP00000264833.3	O95897
	OLFM2	ENST00000593091.2	TSL:5	c.389G>A	p.Arg130Gln	missense	Exon 3 of 6	ENSP00000465809.2	K7EKW2
	OLFM2	ENST00000971550.1		c.311G>A	p.Arg104Gln	missense	Exon 3 of 6	ENSP00000641609.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61784 AN: 151888 Hom.: 15422 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.424

GnomAD2 exomes AF: 0.475 AC: 119182 AN: 251110 AF XY: 0.469

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.610

Gnomad ASJ exome AF: 0.525

Gnomad EAS exome AF: 0.297

Gnomad FIN exome AF: 0.554

Gnomad NFE exome AF: 0.540

Gnomad OTH exome AF: 0.509

GnomAD4 exome AF: 0.516 AC: 754682 AN: 1461764 Hom.: 202473 Cov.: 61 AF XY: 0.510 AC XY: 370806 AN XY: 727174

African (AFR) AF: 0.0964 AC: 3228 AN: 33476

American (AMR) AF: 0.600 AC: 26846 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 13582 AN: 26136

East Asian (EAS) AF: 0.300 AC: 11900 AN: 39700

South Asian (SAS) AF: 0.302 AC: 26036 AN: 86256

European-Finnish (FIN) AF: 0.560 AC: 29909 AN: 53412

Middle Eastern (MID) AF: 0.418 AC: 2395 AN: 5724

European-Non Finnish (NFE) AF: 0.550 AC: 611792 AN: 1111956

Other (OTH) AF: 0.480 AC: 28994 AN: 60388

GnomAD4 genome AF: 0.406 AC: 61779 AN: 152004 Hom.: 15418 Cov.: 32 AF XY: 0.406 AC XY: 30132 AN XY: 74288

African (AFR) AF: 0.114 AC: 4711 AN: 41472

American (AMR) AF: 0.546 AC: 8325 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1848 AN: 3472

East Asian (EAS) AF: 0.296 AC: 1529 AN: 5174

South Asian (SAS) AF: 0.305 AC: 1470 AN: 4818

European-Finnish (FIN) AF: 0.532 AC: 5626 AN: 10570

Middle Eastern (MID) AF: 0.410 AC: 119 AN: 290

European-Non Finnish (NFE) AF: 0.544 AC: 36968 AN: 67936

Other (OTH) AF: 0.421 AC: 887 AN: 2106

Alfa AF: 0.488 Hom.: 59565

Bravo AF: 0.397

TwinsUK AF: 0.551 AC: 2044

ALSPAC AF: 0.553 AC: 2130

ESP6500AA AF: 0.128 AC: 564

ESP6500EA AF: 0.549 AC: 4718

ExAC AF: 0.458 AC: 55603

Asia WGS AF: 0.304 AC: 1056 AN: 3478

EpiCase AF: 0.536

EpiControl AF: 0.534

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
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.017
Eigen_PC	Benign	0.031
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.00085	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.63
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.095
Sift	Uncertain	0.015	D
Sift4G	Benign	0.075	T
Polyphen		0.94	P
Vest4		0.050
MPC		0.83
ClinPred		0.018	T
GERP RS		3.9
PromoterAI		0.031	Neutral
Varity_R		0.090
Mutation Taster		=99/1	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: rs2303100; hg19: chr19-9968434; COSMIC: COSV53428887;