1-64009132-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -0.0500

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 -14 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 id is 1238957.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROR1	NM_005012.4	c.92-173C>T		intron_variant		ENST00000371079.6
ROR1	NM_001083592.2	c.92-173C>T		intron_variant
ROR1	XM_011541526.2	c.-98-173C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROR1	ENST00000371079.6	c.92-173C>T		intron_variant		1	NM_005012.4	P1
ROR1	ENST00000371080.5	c.92-173C>T		intron_variant		1
ROR1	ENST00000482426.1	n.126-173C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.858

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.679

Alfa AF: 0.719 Hom.: 5313

Bravo AF: 0.634

Asia WGS AF: 0.828 AC: 2875 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	11
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs285399; hg19: chr1-64474804;