1-64009249-A-G

Variant names:

• chr1-64009249-A-G
• rs12091083
• NM_005012.4:c.92-56A>G

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.92-56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00605 in 1,308,252 control chromosomes in the GnomAD database, including 419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (254 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (165 hom.)
• Consequence: ROR1 NM_005012.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.662

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-64009249-A-G is Benign according to our data. Variant chr1-64009249-A-G is described in ClinVar as [Benign]. Clinvar id is 1260821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR1	NM_005012.4	c.92-56A>G		intron_variant	Intron 1 of 8	ENST00000371079.6	NP_005003.2
ROR1	NM_001083592.2	c.92-56A>G		intron_variant	Intron 1 of 6		NP_001077061.1
ROR1	XM_011541526.2	c.-98-56A>G		intron_variant	Intron 1 of 8		XP_011539828.1
ROR1	XM_017001377.2	c.-250A>G		upstream_gene_variant			XP_016856866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROR1	ENST00000371079.6	c.92-56A>G		intron_variant	Intron 1 of 8	1	NM_005012.4	ENSP00000360120.1
ROR1	ENST00000371080.5	c.92-56A>G		intron_variant	Intron 1 of 6	1		ENSP00000360121.1
ROR1	ENST00000482426.1	n.126-56A>G		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.0297 AC: 4519 AN: 151966 Hom.: 254 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00806

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.00293 AC: 3382 AN: 1156168 Hom.: 165 AF XY: 0.00248 AC XY: 1465 AN XY: 590856

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.00387

Gnomad4 ASJ exome AF: 0.0000415

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000213

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000516

Gnomad4 OTH exome AF: 0.00593

GnomAD4 genome AF: 0.0298 AC: 4530 AN: 152084 Hom.: 254 Cov.: 32 AF XY: 0.0288 AC XY: 2142 AN XY: 74358

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.00805

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0291 Hom.: 19

Bravo AF: 0.0325

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 24, 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	-0.89
CADD	Benign	7.4
DANN	Benign	0.60

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: rs12091083; hg19: chr1-64474921;