rs6732834

Positions:

• chr2-85278479-C-T

Variant summary

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

The NM_031283.3(TCF7L1):​c.442-5016C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 152,278 control chromosomes in the GnomAD database, including 603 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 0.081 (603 hom., cov: 33)
• Consequence: TCF7L1 NM_031283.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF7L1	NM_031283.3	c.442-5016C>T		intron_variant		ENST00000282111.4
TCF7L1	XM_006712109.3	c.442-5016C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF7L1	ENST00000282111.4	c.442-5016C>T		intron_variant		1	NM_031283.3	P1
TCF7L1	ENST00000442813.1	c.-9-5016C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12382 AN: 152160 Hom.: 601 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0798

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.0951

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

GnomAD4 genome AF: 0.0814 AC: 12394 AN: 152278 Hom.: 603 Cov.: 33 AF XY: 0.0823 AC XY: 6128 AN XY: 74462

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0801

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0999

Gnomad4 FIN AF: 0.0734

Gnomad4 NFE AF: 0.0670

Gnomad4 OTH AF: 0.0941

Alfa AF: 0.0705 Hom.: 639

Bravo AF: 0.0835

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.74

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: rs6732834; hg19: chr2-85505602;