1-161984867-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015441.3(OLFML2B):​c.1588G>A​(p.Val530Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,612,654 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. V530L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: OLFML2B NM_015441.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

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

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>A	p.Val530Ile	missense	Exon 7 of 8	NP_056256.1	Q68BL8-1
	OLFML2B	NM_001347700.2		c.1594G>A	p.Val532Ile	missense	Exon 7 of 8	NP_001334629.1
	OLFML2B	NM_001297713.2		c.1591G>A	p.Val531Ile	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>A	p.Val530Ile	missense	Exon 7 of 8	ENSP00000294794.3	Q68BL8-1
	OLFML2B	ENST00000367940.2	TSL:2	c.1591G>A	p.Val531Ile	missense	Exon 7 of 8	ENSP00000356917.2	F2Z3N3
	OLFML2B	ENST00000367938.1	TSL:2	c.37G>A	p.Val13Ile	missense	Exon 1 of 2	ENSP00000356915.1	Q68BL8-2

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150808 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251454 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000233 AC: 34 AN: 1461846 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 727226

African (AFR) AF: 0.0000299 AC: 1 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: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 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: 0.0000261 AC: 29 AN: 1111990

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

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150808 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 73488

African (AFR) AF: 0.00 AC: 0 AN: 40912

American (AMR) AF: 0.00 AC: 0 AN: 15028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.00 AC: 0 AN: 4734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67876

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	0.68	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.8
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.71	N
REVEL	Uncertain	0.59
Sift	Benign	0.040	D
Sift4G	Uncertain	0.029	D
Polyphen		0.89	P
Vest4		0.76
MutPred		0.57		Loss of loop (P = 0.2897)
MVP		0.82
MPC		0.43
ClinPred		0.66	D
GERP RS		4.3
PromoterAI		-0.042	Neutral
Varity_R		0.15
gMVP		0.46
Mutation Taster		=67/33	polymorphism

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; COSMIC: COSV54193595; COSMIC: COSV54193595;