chr1-64050507-A-AT

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR1	NM_005012.4	c.452-165dupT		intron_variant	Intron 3 of 8	ENST00000371079.6	NP_005003.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROR1	ENST00000371079.6	c.452-179_452-178insT		intron_variant	Intron 3 of 8	1	NM_005012.4	ENSP00000360120.1
ROR1	ENST00000371080.5	c.452-179_452-178insT		intron_variant	Intron 3 of 6	1		ENSP00000360121.1
ROR1	ENST00000482426.1	n.486-179_486-178insT		intron_variant	Intron 3 of 5	5

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

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.0269

Gnomad4 ASJ AF: 0.00302

Gnomad4 EAS AF: 0.0274

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.00801

Gnomad4 NFE AF: 0.00961

Gnomad4 OTH AF: 0.0381

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs397973977; hg19: chr1-64516179;