rs7580690

Variant names:

• chr2-85253299-T-C
• rs7580690
• NM_031283.3:c.442-30196T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-85253299-T-C
• chr2-85253299-T-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.442-30196T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,282 control chromosomes in the GnomAD database, including 3,510 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 0.21 (3510 hom., cov: 29)
• Consequence: TCF7L1 NM_031283.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L1	NM_031283.3	c.442-30196T>C		intron_variant	Intron 3 of 11	ENST00000282111.4	NP_112573.1
TCF7L1	XM_006712109.3	c.442-30196T>C		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.442-30196T>C		intron_variant	Intron 3 of 11	1	NM_031283.3	ENSP00000282111.3
TCF7L1	ENST00000442813.1	c.-10+19411T>C		intron_variant	Intron 4 of 5	5		ENSP00000388984.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31777 AN: 151164 Hom.: 3508 Cov.: 29

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0805

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.210 AC: 31806 AN: 151282 Hom.: 3510 Cov.: 29 AF XY: 0.208 AC XY: 15324 AN XY: 73822

African (AFR) AF: 0.209 AC: 8613 AN: 41158

American (AMR) AF: 0.175 AC: 2648 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1014 AN: 3462

East Asian (EAS) AF: 0.0807 AC: 415 AN: 5142

South Asian (SAS) AF: 0.132 AC: 631 AN: 4766

European-Finnish (FIN) AF: 0.233 AC: 2432 AN: 10430

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15407 AN: 67870

Other (OTH) AF: 0.221 AC: 460 AN: 2080

Alfa AF: 0.221 Hom.: 16926

Bravo AF: 0.207

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.68
PhyloP100		-0.20
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: rs7580690; hg19: chr2-85480422;