NM_144498.4:c.-129+12C>T

Variant names:

• chr20-62238609-C-T
• rs60622969
• NM_144498.4:c.-129+12C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144498.4(OSBPL2):​c.-129+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 148,048 control chromosomes in the GnomAD database, including 11,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11617 hom., cov: 29)
  • Exomes 𝑓: 0.40 (1 hom.)
• Consequence: OSBPL2 NM_144498.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.362
• Publications: 2 publications found

Genes affected

OSBPL2 (HGNC:15761): (oxysterol binding protein like 2) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain, although the encoded protein contains only the sterol-binding domain. In vitro studies have shown that the encoded protein can bind strongly to phosphatic acid and weakly to phosphatidylinositol 3-phosphate, but cannot bind to 25-hydroxycholesterol. The protein associates with the Golgi apparatus. Transcript variants encoding different isoforms have been described. [provided by RefSeq, Sep 2014]

OSBPL2 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 67

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 20-62238609-C-T is Benign according to our data. Variant chr20-62238609-C-T is described in ClinVar as Benign. ClinVar VariationId is 1301807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144498.4. 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
	OSBPL2	NM_144498.4	MANE Select	c.-129+12C>T		intron	N/A	NP_653081.1	Q9H1P3-1
	OSBPL2	NM_014835.5		c.-129+12C>T		intron	N/A	NP_055650.1	Q9H1P3-2
	OSBPL2	NM_001363878.2		c.-495+12C>T		intron	N/A	NP_001350807.1	A0A2R8YDU7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL2	ENST00000313733.9	TSL:1 MANE Select	c.-129+12C>T		intron	N/A	ENSP00000316649.3	Q9H1P3-1
	OSBPL2	ENST00000358053.3	TSL:1	c.-129+12C>T		intron	N/A	ENSP00000350755.2	Q9H1P3-2
	OSBPL2	ENST00000917729.1		c.-585C>T		5_prime_UTR	Exon 1 of 14	ENSP00000587788.1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 55075 AN: 147910 Hom.: 11618 Cov.: 29

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.400

GnomAD4 exome AF: 0.400 AC: 12 AN: 30 Hom.: 1 Cov.: 0 AF XY: 0.318 AC XY: 7 AN XY: 22

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.429 AC: 12 AN: 28

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.372 AC: 55088 AN: 148018 Hom.: 11617 Cov.: 29 AF XY: 0.375 AC XY: 27035 AN XY: 72096

African (AFR) AF: 0.147 AC: 6009 AN: 40998

American (AMR) AF: 0.462 AC: 6916 AN: 14972

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1531 AN: 3402

East Asian (EAS) AF: 0.501 AC: 2493 AN: 4974

South Asian (SAS) AF: 0.453 AC: 2175 AN: 4806

European-Finnish (FIN) AF: 0.420 AC: 3934 AN: 9356

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.461 AC: 30559 AN: 66252

Other (OTH) AF: 0.405 AC: 836 AN: 2066

Alfa AF: 0.404 Hom.: 1653

Bravo AF: 0.368

Asia WGS AF: 0.490 AC: 1457 AN: 2970

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.3
DANN	Benign	0.97
PhyloP100		0.36
PromoterAI		0.077	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs60622969; hg19: chr20-60813665;