rs756876

chr22-20992430-A-C

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.1149+61A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 1,510,680 control chromosomes in the GnomAD database, including 292,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (29730 hom., cov: 33)
  • Exomes 𝑓: 0.62 (262705 hom.)
• Consequence: LZTR1 NM_006767.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.297

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=-0.94).
• BP6: Variant 22-20992430-A-C is Benign according to our data. Variant chr22-20992430-A-C is described in ClinVar as [Benign]. Clinvar id is 561414.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LZTR1	NM_006767.4	c.1149+61A>C		intron_variant		ENST00000646124.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LZTR1	ENST00000646124.2	c.1149+61A>C		intron_variant			NM_006767.4	P1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94501 AN: 151882 Hom.: 29698 Cov.: 33

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.632

GnomAD4 exome AF: 0.620 AC: 841750 AN: 1358680 Hom.: 262705 Cov.: 21 AF XY: 0.615 AC XY: 413063 AN XY: 672020

Gnomad4 AFR exome AF: 0.620

Gnomad4 AMR exome AF: 0.787

Gnomad4 ASJ exome AF: 0.589

Gnomad4 EAS exome AF: 0.616

Gnomad4 SAS exome AF: 0.460

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.629

Gnomad4 OTH exome AF: 0.610

GnomAD4 genome AF: 0.622 AC: 94583 AN: 152000 Hom.: 29730 Cov.: 33 AF XY: 0.618 AC XY: 45900 AN XY: 74280

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.715

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.629

Alfa AF: 0.615 Hom.: 33227

Bravo AF: 0.641

Asia WGS AF: 0.533 AC: 1851 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	-0.94
Cadd	Benign	7.2
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs756876; hg19: chr22-21346719; COSMIC: COSV53145677; COSMIC: COSV53145677;