rs77172590

Variant names:

• chr10-112950260-G-T
• rs77172590
• NM_001367943.1:c.-497G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-112950260-G-T
• chr10-112950260-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001367943.1(TCF7L2):​c.-497G>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0304 in 186,790 control chromosomes in the GnomAD database, including 309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (291 hom., cov: 26)
  • Exomes 𝑓: 0.011 (18 hom.)
• Consequence: TCF7L2 NM_001367943.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.00
• Publications: 5 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, STRONG Submitted by: G2P, PanelApp Australia
• 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=-0.23).
• BP6: Variant 10-112950260-G-T is Benign according to our data. Variant chr10-112950260-G-T is described in ClinVar as Benign. ClinVar VariationId is 1222749.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367943.1. 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
	TCF7L2	NM_001367943.1	MANE Select	c.-497G>T		5_prime_UTR	Exon 1 of 15	NP_001354872.1	Q9NQB0-1
	TCF7L2	NM_001146274.2		c.-497G>T		5_prime_UTR	Exon 1 of 14	NP_001139746.1	Q9NQB0-7
	TCF7L2	NM_030756.5		c.-497G>T		5_prime_UTR	Exon 1 of 14	NP_110383.2	Q9NQB0-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L2	ENST00000355995.9	TSL:1 MANE Select	c.-497G>T		5_prime_UTR	Exon 1 of 15	ENSP00000348274.4	Q9NQB0-1
	TCF7L2	ENST00000627217.3	TSL:1	c.-497G>T		5_prime_UTR	Exon 1 of 14	ENSP00000486891.1	Q9NQB0-7
	TCF7L2	ENST00000538897.5	TSL:1	c.-497G>T		5_prime_UTR	Exon 1 of 14	ENSP00000446172.1	Q9NQB0-6

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 5181 AN: 142276 Hom.: 288 Cov.: 26

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00136

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00775

Gnomad NFE AF: 0.000584

Gnomad OTH AF: 0.0289

GnomAD4 exome AF: 0.0107 AC: 477 AN: 44440 Hom.: 18 Cov.: 0 AF XY: 0.0104 AC XY: 221 AN XY: 21226

African (AFR) AF: 0.143 AC: 257 AN: 1800

American (AMR) AF: 0.0174 AC: 23 AN: 1322

Ashkenazi Jewish (ASJ) AF: 0.0450 AC: 114 AN: 2532

East Asian (EAS) AF: 0.00 AC: 0 AN: 7136

South Asian (SAS) AF: 0.00 AC: 0 AN: 1070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 134

Middle Eastern (MID) AF: 0.0119 AC: 3 AN: 252

European-Non Finnish (NFE) AF: 0.000747 AC: 20 AN: 26786

Other (OTH) AF: 0.0176 AC: 60 AN: 3408

GnomAD4 genome AF: 0.0366 AC: 5204 AN: 142350 Hom.: 291 Cov.: 26 AF XY: 0.0361 AC XY: 2466 AN XY: 68338

African (AFR) AF: 0.124 AC: 4787 AN: 38452

American (AMR) AF: 0.0156 AC: 203 AN: 13042

Ashkenazi Jewish (ASJ) AF: 0.0326 AC: 112 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 4670

South Asian (SAS) AF: 0.000907 AC: 4 AN: 4412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8408

Middle Eastern (MID) AF: 0.00826 AC: 2 AN: 242

European-Non Finnish (NFE) AF: 0.000584 AC: 39 AN: 66796

Other (OTH) AF: 0.0287 AC: 57 AN: 1984

Alfa AF: 0.0176 Hom.: 50

Bravo AF: 0.0407

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Benign	0.95
PhyloP100		4.0
PromoterAI		-0.099	Neutral
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs77172590; hg19: chr10-114710019;