rs12039519

Positions:

• chr1-161983610-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015441.3(OLFML2B):​c.*65C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 1,524,914 control chromosomes in the GnomAD database, including 2,688 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.082 (1165 hom., cov: 32)
  • Exomes 𝑓: 0.027 (1523 hom.)
• Consequence: OLFML2B NM_015441.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLFML2B	NM_015441.3	c.*65C>T		3_prime_UTR_variant	8/8	ENST00000294794.8	NP_056256.1
OLFML2B	NM_001347700.2	c.*65C>T		3_prime_UTR_variant	8/8		NP_001334629.1
OLFML2B	NM_001297713.2	c.*65C>T		3_prime_UTR_variant	8/8		NP_001284642.1
OLFML2B	XM_011509398.3	c.*65C>T		3_prime_UTR_variant	5/5		XP_011507700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLFML2B	ENST00000294794.8	c.*65C>T		3_prime_UTR_variant	8/8	1	NM_015441.3	ENSP00000294794.3

Frequencies

GnomAD3 genomes AF: 0.0819 AC: 12431 AN: 151784 Hom.: 1166 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0571

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0302

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0707

GnomAD4 exome AF: 0.0273 AC: 37473 AN: 1373012 Hom.: 1523 Cov.: 26 AF XY: 0.0265 AC XY: 17865 AN XY: 675042

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.0684

Gnomad4 ASJ exome AF: 0.00791

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.0281

Gnomad4 FIN exome AF: 0.0207

Gnomad4 NFE exome AF: 0.0169

Gnomad4 OTH exome AF: 0.0359

GnomAD4 genome AF: 0.0819 AC: 12444 AN: 151902 Hom.: 1165 Cov.: 32 AF XY: 0.0797 AC XY: 5911 AN XY: 74210

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.0570

Gnomad4 ASJ AF: 0.00750

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0300

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0162

Gnomad4 OTH AF: 0.0742

Alfa AF: 0.0533 Hom.: 76

Bravo AF: 0.0918

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.83

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: rs12039519; hg19: chr1-161953400; COSMIC: COSV54196788;