1-63917718-C-G

Variant names:

• chr1-63917718-C-G
• rs3861946
• NM_005012.4:c.92-91587C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005012.4(ROR1):​c.92-91587C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: ROR1 NM_005012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR1	NM_005012.4	c.92-91587C>G		intron_variant	Intron 1 of 8	ENST00000371079.6	NP_005003.2
ROR1	NM_001083592.2	c.92-91587C>G		intron_variant	Intron 1 of 6		NP_001077061.1
ROR1	XM_011541526.2	c.-99+26226C>G		intron_variant	Intron 1 of 8		XP_011539828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROR1	ENST00000371079.6	c.92-91587C>G		intron_variant	Intron 1 of 8	1	NM_005012.4	ENSP00000360120.1
ROR1	ENST00000371080.5	c.92-91587C>G		intron_variant	Intron 1 of 6	1		ENSP00000360121.1
ROR1	ENST00000482426.1	n.126-91587C>G		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.4
DANN	Benign	0.70
PhyloP100		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3861946; hg19: chr1-64383389;