2-85287594-A-G

Position:

• chr2-85287594-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031283.3(TCF7L1):​c.525+4016A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,248 control chromosomes in the GnomAD database, including 2,612 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 0.13 (2612 hom., cov: 32)
• Consequence: TCF7L1 NM_031283.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257

Genes affected

TCF7L1 (HGNC:11640): (transcription factor 7 like 1) This gene encodes a member of the T cell factor/lymphoid enhancer factor family of transcription factors. These transcription factors are activated by beta catenin, mediate the Wnt signaling pathway and are antagonized by the transforming growth factor beta signaling pathway. The encoded protein contains a high mobility group-box DNA binding domain and participates in the regulation of cell cycle genes and cellular senescence. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L1	NM_031283.3	c.525+4016A>G		intron_variant		ENST00000282111.4	NP_112573.1
TCF7L1	XM_006712109.3	c.525+4016A>G		intron_variant			XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4	c.525+4016A>G		intron_variant		1	NM_031283.3	ENSP00000282111.3
TCF7L1	ENST00000442813.1	c.75+4016A>G		intron_variant		5		ENSP00000388984.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19945 AN: 152130 Hom.: 2607 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0768

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.131 AC: 19987 AN: 152248 Hom.: 2612 Cov.: 32 AF XY: 0.130 AC XY: 9674 AN XY: 74462

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0769

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0336

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0860 Hom.: 378

Bravo AF: 0.151

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.5
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs6719271; hg19: chr2-85514717;