chr1-51795458-G-A

Variant names:

• chr1-51795458-G-A
• rs856613
• NM_001101662.2:c.2605-604C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001101662.2(NRDC):​c.2605-604C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 217,812 control chromosomes in the GnomAD database, including 4,390 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 0.17 (4042 hom., cov: 32)
  • Exomes 𝑓: 0.077 (348 hom.)
• Consequence: NRDC NM_001101662.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450
• Publications: 5 publications found

Genes affected

NRDC (HGNC:7995): (nardilysin convertase) This gene encodes a zinc-dependent endopeptidase that cleaves peptide substrates at the N-terminus of arginine residues in dibasic moieties and is a member of the peptidase M16 family. This protein interacts with heparin-binding EGF-like growth factor and plays a role in cell migration and proliferation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

ENSG00000266993 (HGNC:):

OSBPL9 (HGNC:16386): (oxysterol binding protein like 9) 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 some members contain only the sterol-binding domain. This family member functions as a cholesterol transfer protein that regulates Golgi structure and function. Multiple transcript variants, most of which encode distinct isoforms, have been identified. Related pseudogenes have been identified on chromosomes 3, 11 and 12. [provided by RefSeq, Jul 2010]

OSBPL9 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRDC	NM_001101662.2	c.2605-604C>T		intron_variant	Intron 22 of 30	ENST00000352171.12	NP_001095132.1
NRDC	NM_002525.3	c.2809-604C>T		intron_variant	Intron 24 of 32		NP_002516.2
NRDC	NM_001242361.2	c.2413-604C>T		intron_variant	Intron 24 of 32		NP_001229290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRDC	ENST00000352171.12	c.2605-604C>T		intron_variant	Intron 22 of 30	1	NM_001101662.2	ENSP00000262679.8

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25985 AN: 152010 Hom.: 4028 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0360

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.0771 AC: 5062 AN: 65684 Hom.: 348 Cov.: 3 AF XY: 0.0744 AC XY: 2657 AN XY: 35706

African (AFR) AF: 0.396 AC: 968 AN: 2442

American (AMR) AF: 0.0782 AC: 446 AN: 5704

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 162 AN: 1526

East Asian (EAS) AF: 0.00936 AC: 43 AN: 4596

South Asian (SAS) AF: 0.0495 AC: 470 AN: 9504

European-Finnish (FIN) AF: 0.0420 AC: 83 AN: 1974

Middle Eastern (MID) AF: 0.170 AC: 32 AN: 188

European-Non Finnish (NFE) AF: 0.0715 AC: 2624 AN: 36686

Other (OTH) AF: 0.0764 AC: 234 AN: 3064

GnomAD4 genome AF: 0.171 AC: 26039 AN: 152128 Hom.: 4042 Cov.: 32 AF XY: 0.167 AC XY: 12410 AN XY: 74380

African (AFR) AF: 0.415 AC: 17202 AN: 41446

American (AMR) AF: 0.104 AC: 1586 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 418 AN: 3472

East Asian (EAS) AF: 0.00908 AC: 47 AN: 5178

South Asian (SAS) AF: 0.0685 AC: 330 AN: 4816

European-Finnish (FIN) AF: 0.0360 AC: 382 AN: 10606

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.0816 AC: 5552 AN: 67998

Other (OTH) AF: 0.155 AC: 327 AN: 2112

Alfa AF: 0.109 Hom.: 2419

Bravo AF: 0.188

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.58
PhyloP100		0.045
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: rs856613; hg19: chr1-52261130;