NM_001367943.1:c.-345delC

Variant names:

• chr10-112950403-TC-T
• rs113102683
• NM_001367943.1:c.-345delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001367943.1(TCF7L2):​c.-345delC variant causes a 5 prime UTR change. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (18348 hom., cov: 0)
  • Exomes 𝑓: 0.31 (4378 hom.)
• Consequence: TCF7L2 NM_001367943.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.67
• Publications: 2 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

ENSG00000233547 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 10-112950403-TC-T is Benign according to our data. Variant chr10-112950403-TC-T is described in ClinVar as Benign. ClinVar VariationId is 1276639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 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.-345delC		5_prime_UTR	Exon 1 of 15	NP_001354872.1	Q9NQB0-1
	TCF7L2	NM_001146274.2		c.-345delC		5_prime_UTR	Exon 1 of 14	NP_001139746.1	Q9NQB0-7
	TCF7L2	NM_030756.5		c.-345delC		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.-345delC		5_prime_UTR	Exon 1 of 15	ENSP00000348274.4	Q9NQB0-1
	TCF7L2	ENST00000627217.3	TSL:1	c.-345delC		5_prime_UTR	Exon 1 of 14	ENSP00000486891.1	Q9NQB0-7
	TCF7L2	ENST00000538897.5	TSL:1	c.-345delC		5_prime_UTR	Exon 1 of 14	ENSP00000446172.1	Q9NQB0-6

Frequencies

GnomAD3 genomes AF: 0.503 AC: 70142 AN: 139412 Hom.: 18336 Cov.: 0

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.0622

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.537

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.529

GnomAD4 exome AF: 0.305 AC: 16897 AN: 55320 Hom.: 4378 Cov.: 0 AF XY: 0.299 AC XY: 8127 AN XY: 27192

African (AFR) AF: 0.420 AC: 685 AN: 1630

American (AMR) AF: 0.283 AC: 505 AN: 1782

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1169 AN: 2700

East Asian (EAS) AF: 0.0476 AC: 425 AN: 8924

South Asian (SAS) AF: 0.136 AC: 526 AN: 3854

European-Finnish (FIN) AF: 0.138 AC: 107 AN: 778

Middle Eastern (MID) AF: 0.444 AC: 112 AN: 252

European-Non Finnish (NFE) AF: 0.380 AC: 11958 AN: 31504

Other (OTH) AF: 0.362 AC: 1410 AN: 3896

GnomAD4 genome AF: 0.503 AC: 70158 AN: 139436 Hom.: 18348 Cov.: 0 AF XY: 0.494 AC XY: 33118 AN XY: 67052

African (AFR) AF: 0.537 AC: 19970 AN: 37160

American (AMR) AF: 0.501 AC: 7010 AN: 13990

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1838 AN: 3400

East Asian (EAS) AF: 0.0624 AC: 301 AN: 4822

South Asian (SAS) AF: 0.362 AC: 1512 AN: 4178

European-Finnish (FIN) AF: 0.424 AC: 3120 AN: 7358

Middle Eastern (MID) AF: 0.533 AC: 145 AN: 272

European-Non Finnish (NFE) AF: 0.530 AC: 34718 AN: 65452

Other (OTH) AF: 0.527 AC: 1013 AN: 1924

Alfa AF: 0.331 Hom.: 692

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
PhyloP100		4.7
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: rs113102683; hg19: chr10-114710162; COSMIC: COSV60501267; COSMIC: COSV60501267;