rs178290

chr22-20990616-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006767.4(LZTR1):c.791+91A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,359,724 control chromosomes in the GnomAD database, including 389,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.74 (41671 hom., cov: 33)
  • Exomes 𝑓: 0.76 (348206 hom.)
• Consequence: LZTR1 NM_006767.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.904

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-20990616-A-G is Benign according to our data. Variant chr22-20990616-A-G is described in ClinVar as [Benign]. Clinvar id is 561412.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LZTR1	NM_006767.4	c.791+91A>G		intron_variant		ENST00000646124.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LZTR1	ENST00000646124.2	c.791+91A>G		intron_variant			NM_006767.4	P1

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112158 AN: 152012 Hom.: 41636 Cov.: 33

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.756

GnomAD4 exome AF: 0.758 AC: 915037 AN: 1207594 Hom.: 348206 Cov.: 16 AF XY: 0.753 AC XY: 452278 AN XY: 600566

Gnomad4 AFR exome AF: 0.691

Gnomad4 AMR exome AF: 0.870

Gnomad4 ASJ exome AF: 0.745

Gnomad4 EAS exome AF: 0.781

Gnomad4 SAS exome AF: 0.610

Gnomad4 FIN exome AF: 0.696

Gnomad4 NFE exome AF: 0.770

Gnomad4 OTH exome AF: 0.745

GnomAD4 genome AF: 0.738 AC: 112244 AN: 152130 Hom.: 41671 Cov.: 33 AF XY: 0.735 AC XY: 54666 AN XY: 74360

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.758

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.754

Alfa AF: 0.745 Hom.: 8602

Bravo AF: 0.754

Asia WGS AF: 0.680 AC: 2363 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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	-0.89
Cadd	Benign	1.3
Dann	Benign	0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs178290; hg19: chr22-21344905; COSMIC: COSV104394195; COSMIC: COSV104394195;