rs898518

Variant names:

• chr4-108095668-C-A
• rs898518
• NM_016269.5:c.415-6411G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-108095668-C-A
• chr4-108095668-C-G
• chr4-108095668-C-T

Variant summary

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

The NM_016269.5(LEF1):​c.415-6411G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,002 control chromosomes in the GnomAD database, including 25,176 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 0.57 (25176 hom., cov: 32)
• Consequence: LEF1 NM_016269.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 32 publications found

Genes affected

LEF1 (HGNC:6551): (lymphoid enhancer binding factor 1) This gene encodes a transcription factor belonging to a family of proteins that share homology with the high mobility group protein-1. The protein encoded by this gene can bind to a functionally important site in the T-cell receptor-alpha enhancer, thereby conferring maximal enhancer activity. This transcription factor is involved in the Wnt signaling pathway, and it may function in hair cell differentiation and follicle morphogenesis. Mutations in this gene have been found in somatic sebaceous tumors. This gene has also been linked to other cancers, including androgen-independent prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016269.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEF1	NM_016269.5	MANE Select	c.415-6411G>T		intron	N/A	NP_057353.1	Q9UJU2-1
	LEF1	NM_001130714.3		c.415-6411G>T		intron	N/A	NP_001124186.1	Q9UJU2-6
	LEF1	NM_001130713.3		c.415-6411G>T		intron	N/A	NP_001124185.1	Q9UJU2-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEF1	ENST00000265165.6	TSL:1 MANE Select	c.415-6411G>T		intron	N/A	ENSP00000265165.1	Q9UJU2-1
	LEF1	ENST00000379951.6	TSL:1	c.415-6411G>T		intron	N/A	ENSP00000369284.2	Q9UJU2-6
	LEF1	ENST00000438313.6	TSL:1	c.415-6411G>T		intron	N/A	ENSP00000406176.2	Q9UJU2-5

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86779 AN: 151884 Hom.: 25140 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.572 AC: 86878 AN: 152002 Hom.: 25176 Cov.: 32 AF XY: 0.565 AC XY: 41999 AN XY: 74298

African (AFR) AF: 0.589 AC: 24432 AN: 41476

American (AMR) AF: 0.508 AC: 7764 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2485 AN: 3470

East Asian (EAS) AF: 0.337 AC: 1735 AN: 5146

South Asian (SAS) AF: 0.533 AC: 2573 AN: 4826

European-Finnish (FIN) AF: 0.528 AC: 5578 AN: 10556

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40171 AN: 67942

Other (OTH) AF: 0.612 AC: 1292 AN: 2110

Alfa AF: 0.583 Hom.: 109477

Bravo AF: 0.569

Asia WGS AF: 0.471 AC: 1641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.44
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs898518; hg19: chr4-109016824;