Genetic Variant ROR1:c.-24G>A (chr1-63774394-G-A) – 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.-24G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 1,255,210 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 103 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 55 hom. )

Consequence

ROR1
NM_005012.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.724

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=-0.52).

BP6

Variant 1-63774394-G-A is Benign according to our data. Variant chr1-63774394-G-A is described in ClinVar as [Benign]. Clinvar id is 1235539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR1	NM_005012.4 link	c.-24G>A		5_prime_UTR_variant	Exon 1 of 9	ENST00000371079.6	NP_005003.2	Q01973-1
ROR1	NM_001083592.2 link	c.-24G>A		5_prime_UTR_variant	Exon 1 of 7		NP_001077061.1	Q01973-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROR1	ENST00000371079 link	c.-24G>A		5_prime_UTR_variant	Exon 1 of 9	1	NM_005012.4	ENSP00000360120.1		Q01973-1
ROR1	ENST00000371080 link	c.-24G>A		5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000360121.1		Q01973-3

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

2977

AN:

151280

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0684

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00652

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000251

Gnomad OTH

AF:

0.0145

GnomAD3 exomes

AF:

0.00148

AC:

AN:

29784

Hom.:

AF XY:

0.00133

AC XY:

AN XY:

18058

show subpopulations

Gnomad AFR exome

AF:

0.0659

Gnomad AMR exome

AF:

0.00309

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000830

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00166

AC:

1832

AN:

1103822

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

789

AN XY:

538230

show subpopulations

Gnomad4 AFR exome

AF:

0.0687

Gnomad4 AMR exome

AF:

0.00415

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000113

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000130

Gnomad4 OTH exome

AF:

0.00423

GnomAD4 genome

AF:

0.0197

AC:

2978

AN:

151388

Hom.:

103

Cov.:

AF XY:

0.0189

AC XY:

1400

AN XY:

73984

show subpopulations

Gnomad4 AFR

AF:

0.0682

Gnomad4 AMR

AF:

0.00651

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000251

Gnomad4 OTH

AF:

0.0143

Alfa

AF:

0.0170

Hom.:

Bravo

AF:

0.0224

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 22, 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

-0.52

CADD

Benign

DANN

Benign

0.96

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