rs7085532

Variant names:

• chr10-113099704-G-A
• rs7085532
• NM_001367943.1:c.553-41480G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-113099704-G-A
• chr10-113099704-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.553-41480G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 152,136 control chromosomes in the GnomAD database, including 39,169 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 0.71 (39169 hom., cov: 33)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.867
• Publications: 16 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.553-41480G>A		intron_variant	Intron 5 of 14	ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9	c.553-41480G>A		intron_variant	Intron 5 of 14	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108440 AN: 152018 Hom.: 39123 Cov.: 33

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.713 AC: 108541 AN: 152136 Hom.: 39169 Cov.: 33 AF XY: 0.711 AC XY: 52870 AN XY: 74356

African (AFR) AF: 0.798 AC: 33139 AN: 41512

American (AMR) AF: 0.741 AC: 11325 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2556 AN: 3470

East Asian (EAS) AF: 0.444 AC: 2294 AN: 5168

South Asian (SAS) AF: 0.586 AC: 2823 AN: 4818

European-Finnish (FIN) AF: 0.703 AC: 7437 AN: 10576

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46576 AN: 67986

Other (OTH) AF: 0.702 AC: 1483 AN: 2114

Alfa AF: 0.691 Hom.: 156554

Bravo AF: 0.718

Asia WGS AF: 0.540 AC: 1880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.5
DANN	Benign	0.81
PhyloP100		-0.87
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: rs7085532; hg19: chr10-114859463;