rs1471962

Variant names:

• chr3-45907695-G-C
• rs1471962
• ENST00000827809.1:n.33G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000827809.1(ENSG00000307676):​n.33G>C variant causes a non coding transcript exon 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: ENSG00000307676 ENST00000827809.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.903
• Publications: 6 publications found

Genes affected

ENSG00000307676 (HGNC:):

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=-0.92).
• 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 rank	MANE	Protein	UniProt
LZTFL1	NM_001405920.1	c.27+5425C>G		intron_variant	Intron 2 of 10		NP_001392849.1
LZTFL1	NM_001405921.1	c.27+5425C>G		intron_variant	Intron 2 of 10		NP_001392850.1
LZTFL1	NM_001276378.2	c.-138+5425C>G		intron_variant	Intron 2 of 11		NP_001263307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000307676	ENST00000827809.1	n.33G>C		non_coding_transcript_exon_variant	Exon 1 of 3
LZTFL1	ENST00000539217.5	c.27+5425C>G		intron_variant	Intron 2 of 9	2		ENSP00000441784.1
LZTFL1	ENST00000492333.5	c.-49+5425C>G		intron_variant	Intron 2 of 3	4		ENSP00000505957.1

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

African (AFR) AF: 0.0314 AC: 1305 AN: 41554

American (AMR) AF: 0.0864 AC: 1320 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 570 AN: 3470

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5174

South Asian (SAS) AF: 0.0543 AC: 262 AN: 4824

European-Finnish (FIN) AF: 0.184 AC: 1952 AN: 10582

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11364 AN: 67982

Other (OTH) AF: 0.0863 AC: 182 AN: 2110

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
PhyloP100		0.90
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: rs1471962; hg19: chr3-45949187;