1-64049707-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005012.4(ROR1):c.180C>T(p.Leu60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 1,613,364 control chromosomes in the GnomAD database, including 576,951 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (48726 hom., cov: 30)
  • Exomes 𝑓: 0.85 (528225 hom.)
• Consequence: ROR1 NM_005012.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -5.37

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-64049707-C-T is Benign according to our data. Variant chr1-64049707-C-T is described in ClinVar as [Benign]. Clinvar id is 1240716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROR1	NM_005012.4	c.180C>T	p.Leu60=	synonymous_variant	3/9	ENST00000371079.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROR1	ENST00000371079.6	c.180C>T	p.Leu60=	synonymous_variant	3/9	1	NM_005012.4	P1
ROR1	ENST00000371080.5	c.180C>T	p.Leu60=	synonymous_variant	3/7	1
ROR1	ENST00000482426.1	n.214C>T		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120668 AN: 151882 Hom.: 48692 Cov.: 30

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.871

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.796

GnomAD3 exomes AF: 0.846 AC: 211561 AN: 250144 Hom.: 90134 AF XY: 0.845 AC XY: 114321 AN XY: 135288

Gnomad AFR exome AF: 0.623

Gnomad AMR exome AF: 0.886

Gnomad ASJ exome AF: 0.876

Gnomad EAS exome AF: 0.958

Gnomad SAS exome AF: 0.804

Gnomad FIN exome AF: 0.876

Gnomad NFE exome AF: 0.851

Gnomad OTH exome AF: 0.832

GnomAD4 exome AF: 0.849 AC: 1240676 AN: 1461364 Hom.: 528225 Cov.: 52 AF XY: 0.848 AC XY: 616490 AN XY: 726968

Gnomad4 AFR exome AF: 0.621

Gnomad4 AMR exome AF: 0.879

Gnomad4 ASJ exome AF: 0.878

Gnomad4 EAS exome AF: 0.963

Gnomad4 SAS exome AF: 0.803

Gnomad4 FIN exome AF: 0.876

Gnomad4 NFE exome AF: 0.853

Gnomad4 OTH exome AF: 0.841

GnomAD4 genome AF: 0.794 AC: 120757 AN: 152000 Hom.: 48726 Cov.: 30 AF XY: 0.798 AC XY: 59275 AN XY: 74290

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.848

Gnomad4 ASJ AF: 0.884

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.871

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.797

Alfa AF: 0.835 Hom.: 67639

Bravo AF: 0.788

Asia WGS AF: 0.852 AC: 2960 AN: 3478

EpiCase AF: 0.838

EpiControl AF: 0.838

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Hearing loss, autosomal recessive 108 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.39
Dann	Benign	0.57

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: rs1772626; hg19: chr1-64515379; COSMIC: COSV64285163;