rs35586842

Variant names:

• chr1-64177967-C-T
• rs35586842
• NM_005012.4:c.1926C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-64177967-C-T
• chr1-64177967-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005012.4(ROR1):​c.1926C>T​(p.Ser642Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,614,136 control chromosomes in the GnomAD database, including 302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (156 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (146 hom.)
• Consequence: ROR1 NM_005012.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.01
• Publications: 1 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

ENSG00000303693 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 1-64177967-C-T is Benign according to our data. Variant chr1-64177967-C-T is described in ClinVar as Benign. ClinVar VariationId is 586410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005012.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR1	NM_005012.4	MANE Select	c.1926C>T	p.Ser642Ser	synonymous	Exon 9 of 9	NP_005003.2	Q01973-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR1	ENST00000371079.6	TSL:1 MANE Select	c.1926C>T	p.Ser642Ser	synonymous	Exon 9 of 9	ENSP00000360120.1	Q01973-1
	ENSG00000303693	ENST00000796579.1		n.580-4327G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3763 AN: 152132 Hom.: 156 Cov.: 32

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00864

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0162

GnomAD2 exomes AF: 0.00683 AC: 1713 AN: 250666 AF XY: 0.00495

Gnomad AFR exome AF: 0.0900

Gnomad AMR exome AF: 0.00451

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000372

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00269 AC: 3939 AN: 1461886 Hom.: 146 Cov.: 34 AF XY: 0.00225 AC XY: 1638 AN XY: 727242

African (AFR) AF: 0.0914 AC: 3060 AN: 33478

American (AMR) AF: 0.00503 AC: 225 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00199 AC: 52 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000325 AC: 28 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00433 AC: 25 AN: 5768

European-Non Finnish (NFE) AF: 0.000178 AC: 198 AN: 1112010

Other (OTH) AF: 0.00580 AC: 350 AN: 60396

GnomAD4 genome AF: 0.0248 AC: 3779 AN: 152250 Hom.: 156 Cov.: 32 AF XY: 0.0252 AC XY: 1880 AN XY: 74466

African (AFR) AF: 0.0857 AC: 3559 AN: 41516

American (AMR) AF: 0.00856 AC: 131 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68018

Other (OTH) AF: 0.0165 AC: 35 AN: 2116

Alfa AF: 0.0118 Hom.: 41

Bravo AF: 0.0279

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	ROR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.2
DANN	Benign	0.59
PhyloP100		-2.0
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: rs35586842; hg19: chr1-64643650;