rs3861946

Variant names:

• chr1-63917718-C-A
• rs3861946
• NM_005012.4:c.92-91587C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive 108

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ROR1	NM_005012.4	c.92-91587C>A		intron_variant	Intron 1 of 8	ENST00000371079.6	NP_005003.2
ROR1	NM_001083592.2	c.92-91587C>A		intron_variant	Intron 1 of 6		NP_001077061.1
ROR1	XM_011541526.2	c.-99+26226C>A		intron_variant	Intron 1 of 8		XP_011539828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROR1	ENST00000371079.6	c.92-91587C>A		intron_variant	Intron 1 of 8	1	NM_005012.4	ENSP00000360120.1
ROR1	ENST00000371080.5	c.92-91587C>A		intron_variant	Intron 1 of 6	1		ENSP00000360121.1
ROR1	ENST00000482426.1	n.126-91587C>A		intron_variant	Intron 1 of 5	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

African (AFR) AF: 0.112 AC: 4653 AN: 41450

American (AMR) AF: 0.462 AC: 7055 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1765 AN: 3468

East Asian (EAS) AF: 0.839 AC: 4341 AN: 5172

South Asian (SAS) AF: 0.521 AC: 2514 AN: 4822

European-Finnish (FIN) AF: 0.686 AC: 7237 AN: 10556

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36320 AN: 67988

Other (OTH) AF: 0.446 AC: 940 AN: 2106

Alfa AF: 0.483 Hom.: 42567

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
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3861946; hg19: chr1-64383389;