chr2-85139848-T-G

Variant names:

• chr2-85139848-T-G
• rs6754757
• NM_031283.3:c.441+5398T>G

Variant summary

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

The NM_031283.3(TCF7L1):​c.441+5398T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,894 control chromosomes in the GnomAD database, including 12,808 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 0.41 (12808 hom., cov: 31)
• Consequence: TCF7L1 NM_031283.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• Publications: 5 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L1	NM_031283.3	c.441+5398T>G		intron_variant	Intron 3 of 11	ENST00000282111.4	NP_112573.1
TCF7L1	XM_006712109.3	c.441+5398T>G		intron_variant	Intron 3 of 11		XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4	c.441+5398T>G		intron_variant	Intron 3 of 11	1	NM_031283.3	ENSP00000282111.3
TCF7L1	ENST00000494519.1	n.83+5398T>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61745 AN: 151776 Hom.: 12786 Cov.: 31

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.407 AC: 61815 AN: 151894 Hom.: 12808 Cov.: 31 AF XY: 0.405 AC XY: 30053 AN XY: 74202

African (AFR) AF: 0.403 AC: 16683 AN: 41412

American (AMR) AF: 0.384 AC: 5869 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1503 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1067 AN: 5164

South Asian (SAS) AF: 0.314 AC: 1510 AN: 4806

European-Finnish (FIN) AF: 0.450 AC: 4745 AN: 10544

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.427 AC: 28976 AN: 67918

Other (OTH) AF: 0.393 AC: 830 AN: 2112

Alfa AF: 0.421 Hom.: 27225

Bravo AF: 0.403

Asia WGS AF: 0.275 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.84
PhyloP100		-0.54
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: rs6754757; hg19: chr2-85366971;