chr1-64075704-A-G

Position:

• chr1-64075704-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005012.4(ROR1):​c.482+24988A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,916 control chromosomes in the GnomAD database, including 13,581 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (13581 hom., cov: 32)
• Consequence: ROR1 NM_005012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=4.958).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROR1	NM_005012.4	c.482+24988A>G		intron_variant		ENST00000371079.6	NP_005003.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROR1	ENST00000371079.6	c.482+24988A>G		intron_variant		1	NM_005012.4	ENSP00000360120.1
ROR1	ENST00000371080.5	c.482+24988A>G		intron_variant		1		ENSP00000360121.1
ROR1	ENST00000482426.1	n.516+24988A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55587 AN: 151798 Hom.: 13538 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.297

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.367 AC: 55690 AN: 151916 Hom.: 13581 Cov.: 32 AF XY: 0.358 AC XY: 26615 AN XY: 74274

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.0193

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.303

Alfa AF: 0.327 Hom.: 1259

Bravo AF: 0.379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	5.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1260772; hg19: -;