NM_005012.4:c.482+27034T>G

Variant names:

• chr1-64077750-T-G
• rs1260764
• NM_005012.4:c.482+27034T>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+27034T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,204 control chromosomes in the GnomAD database, including 13,464 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 0.36 (13464 hom., cov: 34)
• Consequence: ROR1 NM_005012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR1	NM_005012.4	c.482+27034T>G		intron_variant	Intron 4 of 8	ENST00000371079.6	NP_005003.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROR1	ENST00000371079.6	c.482+27034T>G		intron_variant	Intron 4 of 8	1	NM_005012.4	ENSP00000360120.1
ROR1	ENST00000371080.5	c.482+27034T>G		intron_variant	Intron 4 of 6	1		ENSP00000360121.1
ROR1	ENST00000482426.1	n.516+27034T>G		intron_variant	Intron 4 of 5	5

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55451 AN: 152086 Hom.: 13424 Cov.: 34

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.365 AC: 55551 AN: 152204 Hom.: 13464 Cov.: 34 AF XY: 0.357 AC XY: 26544 AN XY: 74398

African (AFR) AF: 0.693 AC: 28762 AN: 41522

American (AMR) AF: 0.217 AC: 3324 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 762 AN: 3472

East Asian (EAS) AF: 0.0193 AC: 100 AN: 5184

South Asian (SAS) AF: 0.143 AC: 688 AN: 4826

European-Finnish (FIN) AF: 0.265 AC: 2806 AN: 10588

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18246 AN: 68008

Other (OTH) AF: 0.300 AC: 634 AN: 2112

Alfa AF: 0.190 Hom.: 565

Bravo AF: 0.377

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
PhyloP100		-0.31

Splicing

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

Other links and lift over

dbSNP: rs1260764; hg19: chr1-64543422;