22-20990595-C-T

Variant names:

• chr22-20990595-C-T
• rs2073989
• NM_006767.4:c.791+70C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006767.4(LZTR1):​c.791+70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,476,362 control chromosomes in the GnomAD database, including 84,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6511 hom., cov: 33)
  • Exomes 𝑓: 0.33 (77616 hom.)
• Consequence: LZTR1 NM_006767.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.79

Genes affected

LZTR1 (HGNC:6742): (leucine zipper like post translational regulator 1) This gene encodes a member of the BTB-kelch superfamily. Initially described as a putative transcriptional regulator based on weak homology to members of the basic leucine zipper-like family, the encoded protein subsequently has been shown to localize exclusively to the Golgi network where it may help stabilize the Gogli complex. Deletion of this gene may be associated with DiGeorge syndrome. [provided by RefSeq, Jul 2008]

ENSG00000285314 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-20990595-C-T is Benign according to our data. Variant chr22-20990595-C-T is described in ClinVar as [Benign]. Clinvar id is 561411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LZTR1	NM_006767.4	c.791+70C>T		intron_variant	Intron 8 of 20	ENST00000646124.2	NP_006758.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LZTR1	ENST00000646124.2	c.791+70C>T		intron_variant	Intron 8 of 20		NM_006767.4	ENSP00000496779.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40792 AN: 152030 Hom.: 6500 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.0645

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.332 AC: 439618 AN: 1324214 Hom.: 77616 Cov.: 20 AF XY: 0.328 AC XY: 214643 AN XY: 654534

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.401

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.0834

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.362

Gnomad4 OTH exome AF: 0.319

GnomAD4 genome AF: 0.268 AC: 40807 AN: 152148 Hom.: 6511 Cov.: 33 AF XY: 0.261 AC XY: 19404 AN XY: 74380

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.0643

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.327

Alfa AF: 0.331 Hom.: 12555

Bravo AF: 0.282

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.21
DANN	Benign	0.73
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0

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

LitVar

Other links and lift over

dbSNP: rs2073989; hg19: chr22-21344884; COSMIC: COSV104394210; COSMIC: COSV104394210;