rs756430892

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-161984875-C-A
• chr1-161984875-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015441.3(OLFML2B):​c.1580G>T​(p.Arg527Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R527Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OLFML2B NM_015441.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OLFML2B	NM_015441.3	c.1580G>T	p.Arg527Leu	missense_variant	Exon 7 of 8	ENST00000294794.8	NP_056256.1
OLFML2B	NM_001347700.2	c.1586G>T	p.Arg529Leu	missense_variant	Exon 7 of 8		NP_001334629.1
OLFML2B	NM_001297713.2	c.1583G>T	p.Arg528Leu	missense_variant	Exon 7 of 8		NP_001284642.1
OLFML2B	XM_011509398.3	c.860G>T	p.Arg287Leu	missense_variant	Exon 4 of 5		XP_011507700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLFML2B	ENST00000294794.8	c.1580G>T	p.Arg527Leu	missense_variant	Exon 7 of 8	1	NM_015441.3	ENSP00000294794.3
OLFML2B	ENST00000367940.2	c.1583G>T	p.Arg528Leu	missense_variant	Exon 7 of 8	2		ENSP00000356917.2
OLFML2B	ENST00000367938.1	c.29G>T	p.Arg10Leu	missense_variant	Exon 1 of 2	2		ENSP00000356915.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251462 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135900

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;D;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Uncertain	0.38	D
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.7	D;D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		0.79	P;P;.
Vest4		0.82
MutPred		0.44		.;Loss of ubiquitination at K525 (P = 0.0433);.;
MVP		0.91
MPC		0.59
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.41
gMVP		0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs756430892; hg19: chr1-161954665;