rs4683148

Variant names:

• chr3-45914568-C-T
• rs4683148
• NM_001405920.1:c.-32+853G>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.-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
• Publications: 15 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

ENSG00000307676 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LZTFL1	NM_001405920.1	c.-32+853G>A		intron_variant	Intron 1 of 10		NP_001392849.1
LZTFL1	NM_001405921.1	c.-32+853G>A		intron_variant	Intron 1 of 10		NP_001392850.1
LZTFL1	NM_001276378.2	c.-196+853G>A		intron_variant	Intron 1 of 11		NP_001263307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LZTFL1	ENST00000539217.5	c.-32+853G>A		intron_variant	Intron 1 of 9	2		ENSP00000441784.1
LZTFL1	ENST00000492333.5	c.-107+853G>A		intron_variant	Intron 1 of 3	4		ENSP00000505957.1
LZTFL1	ENST00000472635.5	c.-273+853G>A		intron_variant	Intron 1 of 4	4		ENSP00000506465.1

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

African (AFR) AF: 0.147 AC: 6112 AN: 41480

American (AMR) AF: 0.505 AC: 7718 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3466

East Asian (EAS) AF: 0.652 AC: 3366 AN: 5164

South Asian (SAS) AF: 0.362 AC: 1746 AN: 4828

European-Finnish (FIN) AF: 0.435 AC: 4590 AN: 10550

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26700 AN: 67974

Other (OTH) AF: 0.365 AC: 768 AN: 2104

Alfa AF: 0.382 Hom.: 18937

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
PhyloP100		0.59
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: rs4683148; hg19: chr3-45956060;