Genetic Variant ROR1:c.91+61C>T (chr1-63774569-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.574

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ROR1	NM_005012.4 link	c.91+61C>T		intron_variant	Intron 1 of 8	ENST00000371079.6	NP_005003.2	Q01973-1
ROR1	NM_001083592.2 link	c.91+61C>T		intron_variant	Intron 1 of 6		NP_001077061.1	Q01973-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROR1	ENST00000371079.6 link	c.91+61C>T		intron_variant	Intron 1 of 8	1	NM_005012.4	ENSP00000360120.1		Q01973-1
ROR1	ENST00000371080.5 link	c.91+61C>T		intron_variant	Intron 1 of 6	1		ENSP00000360121.1		Q01973-3

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

49962

AN:

147588

Hom.:

11153

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.337

AC XY:

24205

AN XY:

71926

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over