2-85216801-G-A

Variant names:

• chr2-85216801-G-A
• rs6709476
• NM_031283.3:c.442-66694G>A

Variant summary

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

The NM_031283.3(TCF7L1):​c.442-66694G>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
• Publications: 7 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]

LOC102724579 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031283.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L1	NM_031283.3	MANE Select	c.442-66694G>A		intron	N/A	NP_112573.1
	LOC102724579	NR_136323.1		n.43-219G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L1	ENST00000282111.4	TSL:1 MANE Select	c.442-66694G>A		intron	N/A	ENSP00000282111.3
	TCF7L1	ENST00000442813.1	TSL:5	c.-402-219G>A		intron	N/A	ENSP00000388984.1

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

African (AFR) AF: 0.627 AC: 25943 AN: 41402

American (AMR) AF: 0.215 AC: 3281 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3472

East Asian (EAS) AF: 0.0695 AC: 359 AN: 5162

South Asian (SAS) AF: 0.110 AC: 529 AN: 4812

European-Finnish (FIN) AF: 0.0603 AC: 639 AN: 10592

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0945 AC: 6424 AN: 68002

Other (OTH) AF: 0.215 AC: 453 AN: 2110

Alfa AF: 0.151 Hom.: 11649

Bravo AF: 0.282

Asia WGS AF: 0.154 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.92
DANN	Benign	0.35
PhyloP100		-0.75
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: rs6709476; hg19: chr2-85443924;