chr2-85275141-A-C

Position:

• chr2-85275141-A-C

Variant summary

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

The NM_031283.3(TCF7L1):​c.442-8354A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 152,248 control chromosomes in the GnomAD database, including 58,832 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 0.88 (58832 hom., cov: 32)
• Consequence: TCF7L1 NM_031283.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L1	NM_031283.3	c.442-8354A>C		intron_variant		ENST00000282111.4	NP_112573.1
TCF7L1	XM_006712109.3	c.442-8354A>C		intron_variant			XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4	c.442-8354A>C		intron_variant		1	NM_031283.3	ENSP00000282111.3
TCF7L1	ENST00000442813.1	c.-9-8354A>C		intron_variant		5		ENSP00000388984.1

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133682 AN: 152130 Hom.: 58789 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.879

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

GnomAD4 genome AF: 0.879 AC: 133784 AN: 152248 Hom.: 58832 Cov.: 32 AF XY: 0.879 AC XY: 65420 AN XY: 74458

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.906

Gnomad4 ASJ AF: 0.877

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.912

Gnomad4 FIN AF: 0.845

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.879

Alfa AF: 0.869 Hom.: 79103

Bravo AF: 0.885

Asia WGS AF: 0.920 AC: 3201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.46

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: rs12714137; hg19: chr2-85502264;