1-64137548-G-A

Position:

• chr1-64137548-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005012.4(ROR1):​c.610+52G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,569,140 control chromosomes in the GnomAD database, including 28,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2230 hom., cov: 32)
  • Exomes 𝑓: 0.19 (25985 hom.)
• Consequence: ROR1 NM_005012.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.69

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-64137548-G-A is Benign according to our data. Variant chr1-64137548-G-A is described in ClinVar as [Benign]. Clinvar id is 1242767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROR1	NM_005012.4	c.610+52G>A		intron_variant		ENST00000371079.6	NP_005003.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROR1	ENST00000371079.6	c.610+52G>A		intron_variant		1	NM_005012.4	ENSP00000360120.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24675 AN: 152032 Hom.: 2226 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.152

GnomAD3 exomes AF: 0.157 AC: 35391 AN: 225918 Hom.: 3079 AF XY: 0.163 AC XY: 19888 AN XY: 121952

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0923

Gnomad ASJ exome AF: 0.219

Gnomad EAS exome AF: 0.0339

Gnomad SAS exome AF: 0.150

Gnomad FIN exome AF: 0.149

Gnomad NFE exome AF: 0.200

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.187 AC: 264951 AN: 1416990 Hom.: 25985 Cov.: 25 AF XY: 0.186 AC XY: 130876 AN XY: 701964

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.0990

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.0452

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.162 AC: 24686 AN: 152150 Hom.: 2230 Cov.: 32 AF XY: 0.159 AC XY: 11835 AN XY: 74380

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.0394

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.158

Alfa AF: 0.189 Hom.: 633

Bravo AF: 0.160

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.88
CADD	Benign	7.6
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: rs3738151; hg19: chr1-64603231;