chr4-108125804-G-A

Variant names:

• chr4-108125804-G-A
• rs956237
• NM_016269.5:c.415-36547C>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.415-36547C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,672 control chromosomes in the GnomAD database, including 17,488 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 0.45 (17488 hom., cov: 30)
• Consequence: LEF1 NM_016269.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 21 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEF1	NM_016269.5	MANE Select	c.415-36547C>T		intron	N/A	NP_057353.1
	LEF1	NM_001130714.3		c.415-36547C>T		intron	N/A	NP_001124186.1
	LEF1	NM_001130713.3		c.415-36547C>T		intron	N/A	NP_001124185.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEF1	ENST00000265165.6	TSL:1 MANE Select	c.415-36547C>T		intron	N/A	ENSP00000265165.1
	LEF1	ENST00000379951.6	TSL:1	c.415-36547C>T		intron	N/A	ENSP00000369284.2
	LEF1	ENST00000438313.6	TSL:1	c.415-36547C>T		intron	N/A	ENSP00000406176.2

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68881 AN: 151556 Hom.: 17485 Cov.: 30

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.454 AC: 68907 AN: 151672 Hom.: 17488 Cov.: 30 AF XY: 0.450 AC XY: 33379 AN XY: 74118

African (AFR) AF: 0.230 AC: 9518 AN: 41344

American (AMR) AF: 0.450 AC: 6847 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2477 AN: 3464

East Asian (EAS) AF: 0.318 AC: 1638 AN: 5152

South Asian (SAS) AF: 0.505 AC: 2428 AN: 4804

European-Finnish (FIN) AF: 0.483 AC: 5056 AN: 10468

Middle Eastern (MID) AF: 0.692 AC: 202 AN: 292

European-Non Finnish (NFE) AF: 0.575 AC: 39076 AN: 67902

Other (OTH) AF: 0.516 AC: 1090 AN: 2112

Alfa AF: 0.538 Hom.: 50203

Bravo AF: 0.440

Asia WGS AF: 0.422 AC: 1467 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.55
DANN	Benign	0.76
PhyloP100		-1.1
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: rs956237; hg19: chr4-109046960;