rs4683148

Positions:

• chr3-45914568-C-T

Variant summary

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

The NM_001405920.1(LZTFL1):​c.-32+853G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,046 control chromosomes in the GnomAD database, including 10,748 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 0.35 (10748 hom., cov: 31)
• Consequence: LZTFL1 NM_001405920.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.588

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LZTFL1	NM_001276378.2	c.-196+853G>A		intron_variant			NP_001263307.1
LZTFL1	NM_001276379.2	c.-32+853G>A		intron_variant			NP_001263308.1
LZTFL1	NM_001405920.1	c.-32+853G>A		intron_variant			NP_001392849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LZTFL1	ENST00000472635.5	c.-273+853G>A		intron_variant		4		ENSP00000506465
LZTFL1	ENST00000492333.5	c.-107+853G>A		intron_variant		4		ENSP00000505957
LZTFL1	ENST00000539217.5	c.-32+853G>A		intron_variant		2		ENSP00000441784

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52670 AN: 151928 Hom.: 10732 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.347 AC: 52706 AN: 152046 Hom.: 10748 Cov.: 31 AF XY: 0.353 AC XY: 26264 AN XY: 74318

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.365

Alfa AF: 0.387 Hom.: 15192

Bravo AF: 0.342

Asia WGS AF: 0.507 AC: 1761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4683148; hg19: chr3-45956060;