10-112951110-AC-A

Position:

• chr10-112951110-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001367943.1(TCF7L2):​c.190-89del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,044,480 control chromosomes in the GnomAD database, including 38,180 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4028 hom., cov: 21)
  • Exomes 𝑓: 0.27 (34152 hom.)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.735

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-112951110-AC-A is Benign according to our data. Variant chr10-112951110-AC-A is described in ClinVar as [Benign]. Clinvar id is 1282021.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF7L2	NM_001367943.1	c.190-89del		intron_variant		ENST00000355995.9
LOC124902502	XR_007062291.1	n.566-104del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF7L2	ENST00000355995.9	c.190-89del		intron_variant		1	NM_001367943.1
	ENST00000369391.3	n.99-104del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.235 AC: 33386 AN: 141828 Hom.: 4023 Cov.: 21

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.267 AC: 241343 AN: 902558 Hom.: 34152 Cov.: 5 AF XY: 0.265 AC XY: 120793 AN XY: 455982

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.0622

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.235 AC: 33406 AN: 141922 Hom.: 4028 Cov.: 21 AF XY: 0.234 AC XY: 16168 AN XY: 68976

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.0691

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.239

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs72101402; hg19: chr10-114710869;