rs3861946

Positions:

• chr1-63917718-C-A
• chr1-63917718-C-G
• chr1-63917718-C-T

Variant summary

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

The NM_005012.4(ROR1):​c.92-91587C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,032 control chromosomes in the GnomAD database, including 17,520 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 0.43 (17520 hom., cov: 33)
• Consequence: ROR1 NM_005012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROR1	NM_005012.4	c.92-91587C>A		intron_variant		ENST00000371079.6	NP_005003.2
ROR1	NM_001083592.2	c.92-91587C>A		intron_variant			NP_001077061.1
ROR1	XM_011541526.2	c.-99+26226C>A		intron_variant			XP_011539828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROR1	ENST00000371079.6	c.92-91587C>A		intron_variant		1	NM_005012.4	ENSP00000360120	P1
ROR1	ENST00000371080.5	c.92-91587C>A		intron_variant		1		ENSP00000360121
ROR1	ENST00000482426.1	n.126-91587C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65531 AN: 151914 Hom.: 17527 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.431 AC: 65517 AN: 152032 Hom.: 17520 Cov.: 33 AF XY: 0.443 AC XY: 32928 AN XY: 74298

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.839

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.446

Alfa AF: 0.514 Hom.: 29453

Bravo AF: 0.402

Asia WGS AF: 0.595 AC: 2065 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.2
DANN	Benign	0.71

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: rs3861946; hg19: chr1-64383389;