Genetic Variant NM_005012.4:c.452-165delT (chr1-64050507-AT-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005012.4(ROR1):c.452-165delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 142,736 control chromosomes in the GnomAD database, including 85 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.037 ( 85 hom., cov: 30)

Consequence

ROR1
NM_005012.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.612

Publications

0 publications found

Variant links:

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

ROR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0601 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.452-165delT		intron	N/A	NP_005003.2	Q01973-1
	ROR1	NM_001083592.2		c.452-165delT		intron	N/A	NP_001077061.1	Q01973-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ROR1	ENST00000371079.6	TSL:1 MANE Select	c.452-178delT	intron	N/A	ENSP00000360120.1	Q01973-1
ROR1	ENST00000371080.5	TSL:1	c.452-178delT	intron	N/A	ENSP00000360121.1	Q01973-3
ROR1	ENST00000482426.1	TSL:5	n.486-178delT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0365

AC:

5211

AN:

142710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0410

Gnomad AMI

AF:

0.0788

Gnomad AMR

AF:

0.0280

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.0229

Gnomad SAS

AF:

0.0660

Gnomad FIN

AF:

0.0291

Gnomad MID

AF:

0.0236

Gnomad NFE

AF:

0.0355

Gnomad OTH

AF:

0.0314

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

GnomAD4 genome

AF:

0.0366

AC:

5220

AN:

142736

Hom.:

Cov.:

AF XY:

0.0362

AC XY:

2510

AN XY:

69402

show subpopulations

African (AFR)

AF:

0.0412

AC:

1621

AN:

39346

American (AMR)

AF:

0.0280

AC:

395

AN:

14116

Ashkenazi Jewish (ASJ)

AF:

0.0314

AC:

104

AN:

3308

East Asian (EAS)

AF:

0.0229

AC:

113

AN:

4924

South Asian (SAS)

AF:

0.0663

AC:

294

AN:

4434

European-Finnish (FIN)

AF:

0.0291

AC:

253

AN:

8696

Middle Eastern (MID)

AF:

0.0257

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.0355

AC:

2305

AN:

64844

Other (OTH)

AF:

0.0307

AC:

AN:

1920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

228

456

684

912

1140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00885

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.61

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over