1-63896308-G-C

Variant names:

• chr1-63896308-G-C
• rs855824
• NM_005012.4:c.92-112997G>C

Variant summary

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

The NM_005012.4(ROR1):​c.92-112997G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 151,888 control chromosomes in the GnomAD database, including 56,052 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 0.85 (56052 hom., cov: 32)
• Consequence: ROR1 NM_005012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 2 publications found

Genes affected

ROR1 (HGNC:10256): (receptor tyrosine kinase like orphan receptor 1) This gene encodes a receptor tyrosine kinase-like orphan receptor that modulates neurite growth in the central nervous system. The encoded protein is a glycosylated type I membrane protein that belongs to the ROR subfamily of cell surface receptors. It is a pseudokinase that lacks catalytic activity and may interact with the non-canonical Wnt signalling pathway. This gene is highly expressed during early embryonic development but expressed at very low levels in adult tissues. Increased expression of this gene is associated with B-cell chronic lymphocytic leukaemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2012]

ROR1 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive 108

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005012.4. 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
	ROR1	NM_005012.4	MANE Select	c.92-112997G>C		intron	N/A	NP_005003.2	Q01973-1
	ROR1	NM_001083592.2		c.92-112997G>C		intron	N/A	NP_001077061.1	Q01973-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR1	ENST00000371079.6	TSL:1 MANE Select	c.92-112997G>C		intron	N/A	ENSP00000360120.1	Q01973-1
	ROR1	ENST00000371080.5	TSL:1	c.92-112997G>C		intron	N/A	ENSP00000360121.1	Q01973-3
	ROR1	ENST00000482426.1	TSL:5	n.126-112997G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129204 AN: 151770 Hom.: 56017 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.911

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.865

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.851 AC: 129289 AN: 151888 Hom.: 56052 Cov.: 32 AF XY: 0.854 AC XY: 63432 AN XY: 74250

African (AFR) AF: 0.662 AC: 27383 AN: 41342

American (AMR) AF: 0.914 AC: 13949 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.911 AC: 3160 AN: 3468

East Asian (EAS) AF: 0.997 AC: 5162 AN: 5176

South Asian (SAS) AF: 0.899 AC: 4322 AN: 4810

European-Finnish (FIN) AF: 0.928 AC: 9817 AN: 10584

Middle Eastern (MID) AF: 0.861 AC: 248 AN: 288

European-Non Finnish (NFE) AF: 0.921 AC: 62553 AN: 67940

Other (OTH) AF: 0.870 AC: 1838 AN: 2112

Alfa AF: 0.878 Hom.: 7394

Bravo AF: 0.844

Asia WGS AF: 0.941 AC: 3268 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.093
DANN	Benign	0.43
PhyloP100		-2.8
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: rs855824; hg19: chr1-64361979;