rs1471962

Positions:

• chr3-45907695-G-C
• chr3-45907695-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001405920.1(LZTFL1):​c.27+5425C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,184 control chromosomes in the GnomAD database, including 1,259 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1259 hom., cov: 32)
• Consequence: LZTFL1 NM_001405920.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.903

Genes affected

LZTFL1 (HGNC:6741): (leucine zipper transcription factor like 1) This gene encodes a ubiquitously expressed protein that localizes to the cytoplasm. This protein interacts with Bardet-Biedl Syndrome (BBS) proteins and, through its interaction with BBS protein complexes, regulates protein trafficking to the ciliary membrane. Nonsense mutations in this gene cause a form of Bardet-Biedl Syndrome; a ciliopathy characterized in part by polydactyly, obesity, cognitive impairment, hypogonadism, and kidney failure. This gene may also function as a tumor suppressor; possibly by interacting with E-cadherin and the actin cytoskeleton and thereby regulating the transition of epithelial cells to mesenchymal cells. [provided by RefSeq, Aug 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LZTFL1	NM_001276378.2	c.-138+5425C>G		intron_variant			NP_001263307.1
LZTFL1	NM_001276379.2	c.27+5425C>G		intron_variant			NP_001263308.1
LZTFL1	NM_001405920.1	c.27+5425C>G		intron_variant			NP_001392849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LZTFL1	ENST00000472635.5	c.-215+5425C>G		intron_variant		4		ENSP00000506465
LZTFL1	ENST00000492333.5	c.-49+5425C>G		intron_variant		4		ENSP00000505957
LZTFL1	ENST00000539217.5	c.27+5425C>G		intron_variant		2		ENSP00000441784

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17163 AN: 152066 Hom.: 1260 Cov.: 32

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.0872

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

GnomAD4 genome AF: 0.113 AC: 17164 AN: 152184 Hom.: 1259 Cov.: 32 AF XY: 0.111 AC XY: 8271 AN XY: 74386

Gnomad4 AFR AF: 0.0314

Gnomad4 AMR AF: 0.0864

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0543

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.0863

Alfa AF: 0.0872 Hom.: 134

Bravo AF: 0.102

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1471962; hg19: chr3-45949187;