rs11556087

Variant names:

• chr19-9857463-G-A
• rs11556087
• NM_058164.4:c.380C>T

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.380C>T​(p.Thr127Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,613,302 control chromosomes in the GnomAD database, including 36,008 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2369 hom., cov: 32)
  • Exomes 𝑓: 0.20 (33639 hom.)
• Consequence: OLFM2 NM_058164.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.17
• Publications: 28 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=0.0019342303).
• BP6: Variant 19-9857463-G-A is Benign according to our data. Variant chr19-9857463-G-A is described in ClinVar as Benign. ClinVar VariationId is 1245907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 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.380C>T	p.Thr127Met	missense	Exon 4 of 6	NP_477512.1
	OLFM2	NM_001304347.2		c.452C>T	p.Thr151Met	missense	Exon 4 of 6	NP_001291276.1
	OLFM2	NM_001304348.2		c.146C>T	p.Thr49Met	missense	Exon 3 of 5	NP_001291277.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFM2	ENST00000264833.9	TSL:1 MANE Select	c.380C>T	p.Thr127Met	missense	Exon 4 of 6	ENSP00000264833.3
	OLFM2	ENST00000593091.2	TSL:5	c.452C>T	p.Thr151Met	missense	Exon 4 of 6	ENSP00000465809.2
	OLFM2	ENST00000971550.1		c.371C>T	p.Thr124Met	missense	Exon 4 of 6	ENSP00000641609.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22876 AN: 152046 Hom.: 2371 Cov.: 32

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0400

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.161

GnomAD2 exomes AF: 0.153 AC: 38377 AN: 250354 AF XY: 0.154

Gnomad AFR exome AF: 0.0368

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.280

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.227

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.202 AC: 295778 AN: 1461138 Hom.: 33639 Cov.: 34 AF XY: 0.199 AC XY: 144379 AN XY: 726848

African (AFR) AF: 0.0356 AC: 1191 AN: 33478

American (AMR) AF: 0.105 AC: 4708 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 7054 AN: 26134

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39698

South Asian (SAS) AF: 0.0434 AC: 3745 AN: 86252

European-Finnish (FIN) AF: 0.160 AC: 8513 AN: 53064

Middle Eastern (MID) AF: 0.218 AC: 1258 AN: 5768

European-Non Finnish (NFE) AF: 0.232 AC: 257687 AN: 1111652

Other (OTH) AF: 0.192 AC: 11602 AN: 60380

GnomAD4 genome AF: 0.150 AC: 22858 AN: 152164 Hom.: 2369 Cov.: 32 AF XY: 0.142 AC XY: 10589 AN XY: 74386

African (AFR) AF: 0.0417 AC: 1734 AN: 41542

American (AMR) AF: 0.139 AC: 2125 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5176

South Asian (SAS) AF: 0.0396 AC: 191 AN: 4820

European-Finnish (FIN) AF: 0.145 AC: 1530 AN: 10584

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15800 AN: 67980

Other (OTH) AF: 0.160 AC: 336 AN: 2106

Alfa AF: 0.202 Hom.: 7965

Bravo AF: 0.145

TwinsUK AF: 0.235 AC: 872

ALSPAC AF: 0.244 AC: 942

ESP6500AA AF: 0.0481 AC: 212

ESP6500EA AF: 0.242 AC: 2079

ExAC AF: 0.151 AC: 18288

Asia WGS AF: 0.0250 AC: 86 AN: 3478

EpiCase AF: 0.239

EpiControl AF: 0.236

ClinVar

ClinVar submissions as Germline

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	0.084
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.86	D
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.24
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.020	D
Polyphen		0.99	D
Vest4		0.10
MPC		1.3
ClinPred		0.013	T
GERP RS		4.0
Varity_R		0.035
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: rs11556087; hg19: chr19-9968139; COSMIC: COSV53432583;