rs12022536

chr1-162006444-A-Cchr1-162006444-A-Gchr1-162006444-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015441.3(OLFML2B):c.576T>G(p.Asn192Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,446,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: OLFML2B NM_015441.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05815813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OLFML2B	NM_015441.3	c.576T>G	p.Asn192Lys	missense_variant	4/8	ENST00000294794.8
OLFML2B	NM_001347700.2	c.576T>G	p.Asn192Lys	missense_variant	4/8
OLFML2B	NM_001297713.2	c.576T>G	p.Asn192Lys	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLFML2B	ENST00000294794.8	c.576T>G	p.Asn192Lys	missense_variant	4/8	1	NM_015441.3	P3
OLFML2B	ENST00000367940.2	c.576T>G	p.Asn192Lys	missense_variant	4/8	2		A2

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD3 exomes AF: 0.00000422 AC: 1 AN: 237002 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 128574

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000594

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1446726 Hom.: 0 Cov.: 42 AF XY: 0.00000278 AC XY: 2 AN XY: 719926

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	0.057
Dann	Benign	0.92
DEOGEN2	Benign	0.024	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.060
Sift	Benign	0.16	T;T
Sift4G	Benign	0.11	T;T
Polyphen		0.098	B;P
Vest4		0.41
MutPred		0.20		Gain of ubiquitination at N192 (P = 0.0042);Gain of ubiquitination at N192 (P = 0.0042);
MVP		0.061
MPC		0.23
ClinPred		0.28	T
GERP RS		-8.2
Varity_R		0.15
gMVP		0.16

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: rs12022536; hg19: chr1-161976234;