Variant 1-64009387-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005012.4(ROR1):c.163+11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000395 in 1,598,820 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 3 hom. )

Consequence

ROR1
NM_005012.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.93

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 1-64009387-G-T is Benign according to our data. Variant chr1-64009387-G-T is described in ClinVar as [Benign]. Clinvar id is 1585811.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ROR1	NM_005012.4 linkuse as main transcript	c.163+11G>T	intron_variant	ENST00000371079.6
ROR1	NM_001083592.2 linkuse as main transcript	c.163+11G>T	intron_variant
ROR1	XM_011541526.2 linkuse as main transcript	c.-27+11G>T	intron_variant
ROR1	XM_017001377.2 linkuse as main transcript	c.-123+11G>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ROR1	ENST00000371079.6 linkuse as main transcript	c.163+11G>T	intron_variant	1	NM_005012.4	P1	Q01973-1
ROR1	ENST00000371080.5 linkuse as main transcript	c.163+11G>T	intron_variant	1			Q01973-3
ROR1	ENST00000482426.1 linkuse as main transcript	n.197+11G>T	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00211

AC:

320

AN:

151870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00740

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000594

AC:

149

AN:

250852

Hom.:

AF XY:

0.000421

AC XY:

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.00770

Gnomad AMR exome

AF:

0.000666

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000216

AC:

313

AN:

1446834

Hom.:

Cov.:

AF XY:

0.000178

AC XY:

128

AN XY:

720860

show subpopulations

Gnomad4 AFR exome

AF:

0.00728

Gnomad4 AMR exome

AF:

0.000828

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000273

Gnomad4 OTH exome

AF:

0.000451

GnomAD4 genome

AF:

0.00209

AC:

318

AN:

151986

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

143

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00733

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.00252

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 11, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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