1-64050507-A-AT

Variant names:

• chr1-64050507-A-AT
• rs397973977
• NM_005012.4:c.452-165dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005012.4(ROR1):​c.452-165dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0707 in 142,882 control chromosomes in the GnomAD database, including 957 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.071 (957 hom., cov: 30)
• Consequence: ROR1 NM_005012.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.612
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 1-64050507-A-AT is Benign according to our data. Variant chr1-64050507-A-AT is described in ClinVar as Benign. ClinVar VariationId is 1276857.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 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.452-165dupT		intron	N/A	NP_005003.2	Q01973-1
	ROR1	NM_001083592.2		c.452-165dupT		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.452-179_452-178insT		intron	N/A	ENSP00000360120.1	Q01973-1
	ROR1	ENST00000371080.5	TSL:1	c.452-179_452-178insT		intron	N/A	ENSP00000360121.1	Q01973-3
	ROR1	ENST00000482426.1	TSL:5	n.486-179_486-178insT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0706 AC: 10084 AN: 142854 Hom.: 953 Cov.: 30

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0270

Gnomad ASJ AF: 0.00302

Gnomad EAS AF: 0.0274

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.00801

Gnomad MID AF: 0.0338

Gnomad NFE AF: 0.00959

Gnomad OTH AF: 0.0383

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

GnomAD4 genome AF: 0.0707 AC: 10106 AN: 142882 Hom.: 957 Cov.: 30 AF XY: 0.0693 AC XY: 4812 AN XY: 69466

African (AFR) AF: 0.222 AC: 8748 AN: 39346

American (AMR) AF: 0.0269 AC: 380 AN: 14126

Ashkenazi Jewish (ASJ) AF: 0.00302 AC: 10 AN: 3308

East Asian (EAS) AF: 0.0274 AC: 135 AN: 4922

South Asian (SAS) AF: 0.0126 AC: 56 AN: 4432

European-Finnish (FIN) AF: 0.00801 AC: 70 AN: 8738

Middle Eastern (MID) AF: 0.0368 AC: 10 AN: 272

European-Non Finnish (NFE) AF: 0.00961 AC: 624 AN: 64946

Other (OTH) AF: 0.0381 AC: 73 AN: 1916

Alfa AF: 0.00112 Hom.: 4

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs397973977; hg19: chr1-64516179; COSMIC: COSV64291156;