3-45874730-C-T

Variant names:

• chr3-45874730-C-T
• rs12639224
• NM_001405920.1:c.28-36679G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001405920.1(LZTFL1):​c.28-36679G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,076 control chromosomes in the GnomAD database, including 5,762 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 0.27 (5762 hom., cov: 32)
• Consequence: LZTFL1 NM_001405920.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253
• Publications: 6 publications found

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]

LZTFL1 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Bardet-Biedl syndrome 17

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LZTFL1	NM_001405920.1	c.28-36679G>A		intron_variant	Intron 2 of 10		NP_001392849.1
LZTFL1	NM_001405921.1	c.28-19656G>A		intron_variant	Intron 2 of 10		NP_001392850.1
LZTFL1	NM_001276378.2	c.-137-19656G>A		intron_variant	Intron 2 of 11		NP_001263307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LZTFL1	ENST00000684620.1	c.-138+9933G>A		intron_variant	Intron 1 of 10			ENSP00000506925.1
LZTFL1	ENST00000539217.5	c.28-19656G>A		intron_variant	Intron 2 of 9	2		ENSP00000441784.1
LZTFL1	ENST00000492333.5	c.-48-36679G>A		intron_variant	Intron 2 of 3	4		ENSP00000505957.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40326 AN: 151958 Hom.: 5754 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.265 AC: 40357 AN: 152076 Hom.: 5762 Cov.: 32 AF XY: 0.270 AC XY: 20055 AN XY: 74324

African (AFR) AF: 0.278 AC: 11528 AN: 41478

American (AMR) AF: 0.204 AC: 3117 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1175 AN: 3466

East Asian (EAS) AF: 0.110 AC: 568 AN: 5184

South Asian (SAS) AF: 0.507 AC: 2445 AN: 4824

European-Finnish (FIN) AF: 0.286 AC: 3020 AN: 10554

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17523 AN: 67976

Other (OTH) AF: 0.274 AC: 577 AN: 2108

Alfa AF: 0.268 Hom.: 5931

Bravo AF: 0.253

Asia WGS AF: 0.304 AC: 1056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.40
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12639224; hg19: chr3-45916222;