rs10520406

Variant names:

• chr2-85152929-T-C
• rs10520406
• NM_031283.3:c.441+18479T>C

Variant summary

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

The NM_031283.3(TCF7L1):​c.441+18479T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0736 in 152,264 control chromosomes in the GnomAD database, including 621 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 0.074 (621 hom., cov: 33)
• Consequence: TCF7L1 NM_031283.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 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.441+18479T>C		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.441+18479T>C		intron	N/A	ENSP00000282111.3	Q9HCS4
	TCF7L1	ENST00000922942.1		c.441+18479T>C		intron	N/A	ENSP00000593001.1
	TCF7L1	ENST00000868102.1		c.441+18479T>C		intron	N/A	ENSP00000538161.1

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11166 AN: 152146 Hom.: 613 Cov.: 33

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0656

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

GnomAD4 genome AF: 0.0736 AC: 11208 AN: 152264 Hom.: 621 Cov.: 33 AF XY: 0.0728 AC XY: 5419 AN XY: 74452

African (AFR) AF: 0.149 AC: 6174 AN: 41546

American (AMR) AF: 0.109 AC: 1660 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3466

East Asian (EAS) AF: 0.0208 AC: 108 AN: 5188

South Asian (SAS) AF: 0.0466 AC: 225 AN: 4824

European-Finnish (FIN) AF: 0.0197 AC: 209 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0373 AC: 2536 AN: 68022

Other (OTH) AF: 0.0649 AC: 137 AN: 2110

Alfa AF: 0.0461 Hom.: 722

Bravo AF: 0.0841

Asia WGS AF: 0.0510 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.7
DANN	Benign	0.57
PhyloP100		1.3
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10520406;

hg19: chr2-85380052;