1-162021447-G-A

Variant names:

• chr1-162021447-G-A
• rs4656345
• NM_015441.3:c.175-1265C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015441.3(OLFML2B):​c.175-1265C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 152,274 control chromosomes in the GnomAD database, including 87 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 0.026 (87 hom., cov: 33)
• Consequence: OLFML2B NM_015441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0261 (3981/152274) while in subpopulation NFE AF = 0.039 (2653/68016). AF 95% confidence interval is 0.0378. There are 87 homozygotes in GnomAd4. There are 1960 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 87 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OLFML2B	NM_015441.3	c.175-1265C>T		intron_variant	Intron 1 of 7	ENST00000294794.8	NP_056256.1
OLFML2B	NM_001347700.2	c.175-1265C>T		intron_variant	Intron 1 of 7		NP_001334629.1
OLFML2B	NM_001297713.2	c.175-1265C>T		intron_variant	Intron 1 of 7		NP_001284642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OLFML2B	ENST00000294794.8	c.175-1265C>T		intron_variant	Intron 1 of 7	1	NM_015441.3	ENSP00000294794.3
OLFML2B	ENST00000367940.2	c.175-1265C>T		intron_variant	Intron 1 of 7	2		ENSP00000356917.2

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3980 AN: 152156 Hom.: 87 Cov.: 33

Gnomad AFR AF: 0.00794

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0220

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0261 AC: 3981 AN: 152274 Hom.: 87 Cov.: 33 AF XY: 0.0263 AC XY: 1960 AN XY: 74482

African (AFR) AF: 0.00792 AC: 329 AN: 41556

American (AMR) AF: 0.0297 AC: 454 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4824

European-Finnish (FIN) AF: 0.0419 AC: 445 AN: 10614

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0390 AC: 2653 AN: 68016

Other (OTH) AF: 0.0218 AC: 46 AN: 2112

Alfa AF: 0.0344 Hom.: 145

Bravo AF: 0.0246

Asia WGS AF: 0.00462 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.32
PhyloP100		0.13
Mutation Taster		=100/0	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: rs4656345; hg19: chr1-161991237;