chr1-161984875-C-T

Variant names:

• chr1-161984875-C-T
• rs756430892
• NM_015441.3:c.1580G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015441.3(OLFML2B):​c.1580G>A​(p.Arg527Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,612,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: OLFML2B NM_015441.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 3.21
• Publications: 1 publications found

Genes affected

OLFML2B (HGNC:24558): (olfactomedin like 2B) This gene encodes an olfactomedin domain-containing protein. Most olfactomedin domain-containing proteins are secreted glycoproteins. [provided by RefSeq, Dec 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30183753).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015441.3. 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
	OLFML2B	NM_015441.3	MANE Select	c.1580G>A	p.Arg527Gln	missense	Exon 7 of 8	NP_056256.1	Q68BL8-1
	OLFML2B	NM_001347700.2		c.1586G>A	p.Arg529Gln	missense	Exon 7 of 8	NP_001334629.1
	OLFML2B	NM_001297713.2		c.1583G>A	p.Arg528Gln	missense	Exon 7 of 8	NP_001284642.1	F2Z3N3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLFML2B	ENST00000294794.8	TSL:1 MANE Select	c.1580G>A	p.Arg527Gln	missense	Exon 7 of 8	ENSP00000294794.3	Q68BL8-1
	OLFML2B	ENST00000367940.2	TSL:2	c.1583G>A	p.Arg528Gln	missense	Exon 7 of 8	ENSP00000356917.2	F2Z3N3
	OLFML2B	ENST00000367938.1	TSL:2	c.29G>A	p.Arg10Gln	missense	Exon 1 of 2	ENSP00000356915.1	Q68BL8-2

Frequencies

GnomAD3 genomes AF: 0.0000531 AC: 8 AN: 150540 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000148

Gnomad OTH AF: 0.000486

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251462 AF XY: 0.0000294

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000198 AC: 29 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 727224

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111986

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.0000531 AC: 8 AN: 150540 Hom.: 0 Cov.: 27 AF XY: 0.0000273 AC XY: 2 AN XY: 73300

African (AFR) AF: 0.000147 AC: 6 AN: 40870

American (AMR) AF: 0.00 AC: 0 AN: 15030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5084

South Asian (SAS) AF: 0.00 AC: 0 AN: 4730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67784

Other (OTH) AF: 0.000486 AC: 1 AN: 2056

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.2
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.56
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.13	T
Polyphen		0.59	P
Vest4		0.52
MutPred		0.43		Gain of catalytic residue at R528 (P = 0.0888)
MVP		0.84
MPC		0.38
ClinPred		0.26	T
GERP RS		4.3
PromoterAI		-0.035	Neutral
Varity_R		0.27
gMVP		0.68
Mutation Taster		=89/11	disease causing (ClinVar)

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: rs756430892; hg19: chr1-161954665;