rs285399

Variant names:

• chr1-64009132-C-T
• rs285399
• NM_005012.4:c.92-173C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-64009132-C-T
• chr1-64009132-C-A
• chr1-64009132-C-G

Variant summary

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

The NM_005012.4(ROR1):​c.92-173C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,010 control chromosomes in the GnomAD database, including 37,441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.66 (37441 hom., cov: 31)
• Consequence: ROR1 NM_005012.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0500
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 1-64009132-C-T is Benign according to our data. Variant chr1-64009132-C-T is described in ClinVar as Benign. ClinVar VariationId is 1238957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 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.92-173C>T		intron	N/A	NP_005003.2	Q01973-1
	ROR1	NM_001083592.2		c.92-173C>T		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.92-173C>T		intron	N/A	ENSP00000360120.1	Q01973-1
	ROR1	ENST00000371080.5	TSL:1	c.92-173C>T		intron	N/A	ENSP00000360121.1	Q01973-3
	ROR1	ENST00000482426.1	TSL:5	n.126-173C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99906 AN: 151892 Hom.: 37424 Cov.: 31

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.658 AC: 99950 AN: 152010 Hom.: 37441 Cov.: 31 AF XY: 0.666 AC XY: 49486 AN XY: 74324

African (AFR) AF: 0.265 AC: 10975 AN: 41384

American (AMR) AF: 0.775 AC: 11840 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2619 AN: 3468

East Asian (EAS) AF: 0.942 AC: 4874 AN: 5174

South Asian (SAS) AF: 0.799 AC: 3849 AN: 4816

European-Finnish (FIN) AF: 0.858 AC: 9080 AN: 10588

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54329 AN: 67988

Other (OTH) AF: 0.679 AC: 1434 AN: 2112

Alfa AF: 0.703 Hom.: 5358

Bravo AF: 0.634

Asia WGS AF: 0.828 AC: 2875 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		-0.050
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: rs285399; hg19: chr1-64474804;