rs7081062

Variant names:

• chr10-112980986-G-A
• rs7081062
• NM_001367943.1:c.450+16362G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-112980986-G-A
• chr10-112980986-G-C
• chr10-112980986-G-T

Variant summary

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

The NM_001367943.1(TCF7L2):​c.450+16362G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,098 control chromosomes in the GnomAD database, including 31,069 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 0.64 (31069 hom., cov: 33)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• Publications: 9 publications found

Genes affected

TCF7L2 (HGNC:11641): (transcription factor 7 like 2) This gene encodes a high mobility group (HMG) box-containing transcription factor that plays a key role in the Wnt signaling pathway. The protein has been implicated in blood glucose homeostasis. Genetic variants of this gene are associated with increased risk of type 2 diabetes. Several transcript variants encoding multiple different isoforms have been found for this gene.[provided by RefSeq, Oct 2010]

TCF7L2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• intellectual disability

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• congenital glaucoma

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.450+16362G>A		intron_variant	Intron 4 of 14	ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9	c.450+16362G>A		intron_variant	Intron 4 of 14	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96748 AN: 151980 Hom.: 31045 Cov.: 33

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.637 AC: 96816 AN: 152098 Hom.: 31069 Cov.: 33 AF XY: 0.632 AC XY: 46958 AN XY: 74340

African (AFR) AF: 0.691 AC: 28665 AN: 41504

American (AMR) AF: 0.548 AC: 8368 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2324 AN: 3466

East Asian (EAS) AF: 0.713 AC: 3694 AN: 5178

South Asian (SAS) AF: 0.643 AC: 3104 AN: 4828

European-Finnish (FIN) AF: 0.559 AC: 5900 AN: 10556

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42548 AN: 67966

Other (OTH) AF: 0.667 AC: 1411 AN: 2116

Alfa AF: 0.638 Hom.: 11573

Bravo AF: 0.640

Asia WGS AF: 0.624 AC: 2172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.18
DANN	Benign	0.66
PhyloP100		-0.59
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: rs7081062; hg19: chr10-114740745;