2-85287594-A-G

Variant names:

• chr2-85287594-A-G
• rs6719271
• NM_031283.3:c.525+4016A>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.525+4016A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,248 control chromosomes in the GnomAD database, including 2,612 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 0.13 (2612 hom., cov: 32)
• Consequence: TCF7L1 NM_031283.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 1 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]

TCF7L1 Gene-Disease associations (from GenCC):

• combined pituitary hormone deficiencies, genetic form

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L1	NM_031283.3	MANE Select	c.525+4016A>G		intron	N/A	NP_112573.1	Q9HCS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L1	ENST00000282111.4	TSL:1 MANE Select	c.525+4016A>G		intron	N/A	ENSP00000282111.3	Q9HCS4
	TCF7L1	ENST00000922942.1		c.525+4016A>G		intron	N/A	ENSP00000593001.1
	TCF7L1	ENST00000868102.1		c.525+4016A>G		intron	N/A	ENSP00000538161.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19945 AN: 152130 Hom.: 2607 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0768

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.131 AC: 19987 AN: 152248 Hom.: 2612 Cov.: 32 AF XY: 0.130 AC XY: 9674 AN XY: 74462

African (AFR) AF: 0.334 AC: 13859 AN: 41488

American (AMR) AF: 0.140 AC: 2135 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 186 AN: 3472

East Asian (EAS) AF: 0.104 AC: 540 AN: 5186

South Asian (SAS) AF: 0.0769 AC: 371 AN: 4826

European-Finnish (FIN) AF: 0.0314 AC: 334 AN: 10624

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0336 AC: 2286 AN: 68030

Other (OTH) AF: 0.111 AC: 234 AN: 2116

Alfa AF: 0.0814 Hom.: 2445

Bravo AF: 0.151

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.5
DANN	Benign	0.72
PhyloP100		0.26
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: rs6719271; hg19: chr2-85514717;