rs6709476

Positions:

• chr2-85216801-G-A
• chr2-85216801-G-T

Variant summary

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

The NM_031283.3(TCF7L1):​c.442-66694G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,042 control chromosomes in the GnomAD database, including 9,104 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 0.25 (9104 hom., cov: 32)
• Consequence: TCF7L1 NM_031283.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753

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]

LOC102724579 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L1	NM_031283.3	c.442-66694G>A		intron_variant		ENST00000282111.4	NP_112573.1
LOC102724579	NR_136323.1	n.43-219G>A		intron_variant, non_coding_transcript_variant
TCF7L1	XM_006712109.3	c.442-66694G>A		intron_variant			XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4	c.442-66694G>A		intron_variant		1	NM_031283.3	ENSP00000282111	P1
TCF7L1	ENST00000442813.1	c.-402-219G>A		intron_variant		5		ENSP00000388984

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38077 AN: 151924 Hom.: 9071 Cov.: 32

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0692

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0945

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.251 AC: 38174 AN: 152042 Hom.: 9104 Cov.: 32 AF XY: 0.244 AC XY: 18152 AN XY: 74334

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.0695

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0603

Gnomad4 NFE AF: 0.0945

Gnomad4 OTH AF: 0.215

Alfa AF: 0.119 Hom.: 2742

Bravo AF: 0.282

Asia WGS AF: 0.154 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.92
DANN	Benign	0.35

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: rs6709476; hg19: chr2-85443924;