1-64075704-A-G

Variant names:

• chr1-64075704-A-G
• rs1260772
• NM_005012.4:c.482+24988A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 (Cadd=4.958).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 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.482+24988A>G		intron	N/A	NP_005003.2	Q01973-1
	ROR1	NM_001083592.2		c.482+24988A>G		intron	N/A	NP_001077061.1	Q01973-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR1	ENST00000371079.6	TSL:1 MANE Select	c.482+24988A>G		intron	N/A	ENSP00000360120.1	Q01973-1
	ROR1	ENST00000371080.5	TSL:1	c.482+24988A>G		intron	N/A	ENSP00000360121.1	Q01973-3
	ROR1	ENST00000482426.1	TSL:5	n.516+24988A>G		intron	N/A

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

African (AFR) AF: 0.699 AC: 28934 AN: 41378

American (AMR) AF: 0.218 AC: 3330 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 761 AN: 3466

East Asian (EAS) AF: 0.0193 AC: 100 AN: 5182

South Asian (SAS) AF: 0.143 AC: 689 AN: 4826

European-Finnish (FIN) AF: 0.263 AC: 2780 AN: 10552

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18232 AN: 67930

Other (OTH) AF: 0.303 AC: 639 AN: 2110

Alfa AF: 0.327 Hom.: 1259

Bravo AF: 0.379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	5.0
PhyloP100		-0.0050

Splicing

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

Other links and lift over

dbSNP: rs1260772;