1-161984867-C-A

Variant names:

• chr1-161984867-C-A
• rs749921063
• NM_015441.3:c.1588G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015441.3(OLFML2B):​c.1588G>T​(p.Val530Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OLFML2B NM_015441.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.76
• Publications: 7 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.765

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.1588G>T	p.Val530Leu	missense	Exon 7 of 8	NP_056256.1	Q68BL8-1
	OLFML2B	NM_001347700.2		c.1594G>T	p.Val532Leu	missense	Exon 7 of 8	NP_001334629.1
	OLFML2B	NM_001297713.2		c.1591G>T	p.Val531Leu	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.1588G>T	p.Val530Leu	missense	Exon 7 of 8	ENSP00000294794.3	Q68BL8-1
	OLFML2B	ENST00000367940.2	TSL:2	c.1591G>T	p.Val531Leu	missense	Exon 7 of 8	ENSP00000356917.2	F2Z3N3
	OLFML2B	ENST00000367938.1	TSL:2	c.37G>T	p.Val13Leu	missense	Exon 1 of 2	ENSP00000356915.1	Q68BL8-2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461848 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

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: 0.00000180 AC: 2 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Benign	2.0	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.3	N
REVEL	Pathogenic	0.80
Sift	Benign	0.059	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.75	P
Vest4		0.82
MutPred		0.61		Gain of catalytic residue at V531 (P = 0.0722)
MVP		0.89
MPC		0.45
ClinPred		0.93	D
GERP RS		4.3
PromoterAI		-0.096	Neutral
Varity_R		0.26
gMVP		0.72
Mutation Taster		=47/53	disease causing

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: rs749921063; hg19: chr1-161954657;