1-64050507-ATTT-ATTTTT

Variant names:

• chr1-64050507-A-ATT
• rs397973977
• NM_005012.4:c.452-166_452-165dupTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005012.4(ROR1):​c.452-166_452-165dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000301 in 143,010 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00030 (0 hom., cov: 30)
• Consequence: ROR1 NM_005012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR1	NM_005012.4	c.452-166_452-165dupTT		intron_variant	Intron 3 of 8	ENST00000371079.6	NP_005003.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROR1	ENST00000371079.6	c.452-179_452-178insTT		intron_variant	Intron 3 of 8	1	NM_005012.4	ENSP00000360120.1
ROR1	ENST00000371080.5	c.452-179_452-178insTT		intron_variant	Intron 3 of 6	1		ENSP00000360121.1
ROR1	ENST00000482426.1	n.486-179_486-178insTT		intron_variant	Intron 3 of 5	5

Frequencies

GnomAD3 genomes AF: 0.000294 AC: 42 AN: 142982 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000764

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000708

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00203

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000154

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000301 AC: 43 AN: 143010 Hom.: 0 Cov.: 30 AF XY: 0.000359 AC XY: 25 AN XY: 69546

Gnomad4 AFR AF: 0.000787

Gnomad4 AMR AF: 0.0000707

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00203

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000154

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs397973977; hg19: chr1-64516179;