1-63774569-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.91+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 907,782 control chromosomes in the GnomAD database, including 33,321 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (11207 hom., cov: 29)
  • Exomes 𝑓: 0.23 (22114 hom.)
• Consequence: ROR1 NM_005012.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.574

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=-0.88).
• BP6: Variant 1-63774569-C-T is Benign according to our data. Variant chr1-63774569-C-T is described in ClinVar as [Benign]. Clinvar id is 1268836.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROR1	NM_005012.4	c.91+61C>T		intron_variant		ENST00000371079.6
ROR1	NM_001083592.2	c.91+61C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROR1	ENST00000371079.6	c.91+61C>T		intron_variant		1	NM_005012.4	P1
ROR1	ENST00000371080.5	c.91+61C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 49962 AN: 147588 Hom.: 11153 Cov.: 29

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.299

GnomAD4 exome AF: 0.228 AC: 172945 AN: 760084 Hom.: 22114 AF XY: 0.228 AC XY: 81762 AN XY: 358290

Gnomad4 AFR exome AF: 0.689

Gnomad4 AMR exome AF: 0.207

Gnomad4 ASJ exome AF: 0.251

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.339 AC: 50081 AN: 147698 Hom.: 11207 Cov.: 29 AF XY: 0.337 AC XY: 24205 AN XY: 71926

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.308

Alfa AF: 0.287 Hom.: 1013

Bravo AF: 0.347

Asia WGS AF: 0.298 AC: 892 AN: 3000

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.4
Dann	Benign	0.90

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: rs606550; hg19: chr1-64240240;