rs7917983

Variant names:

• chr10-112973123-T-C
• rs7917983
• NM_001367943.1:c.450+8499T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-112973123-T-C
• chr10-112973123-T-G

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+8499T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,058 control chromosomes in the GnomAD database, including 26,573 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 0.57 (26573 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607
• Publications: 27 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 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.450+8499T>C		intron	N/A	NP_001354872.1	Q9NQB0-1
	TCF7L2	NM_001146274.2		c.450+8499T>C		intron	N/A	NP_001139746.1	Q9NQB0-7
	TCF7L2	NM_030756.5		c.381+21516T>C		intron	N/A	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.450+8499T>C		intron	N/A	ENSP00000348274.4	Q9NQB0-1
	TCF7L2	ENST00000627217.3	TSL:1	c.450+8499T>C		intron	N/A	ENSP00000486891.1	Q9NQB0-7
	TCF7L2	ENST00000369397.8	TSL:1	c.381+21516T>C		intron	N/A	ENSP00000358404.4	Q9NQB0-8

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87066 AN: 151940 Hom.: 26521 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.573 AC: 87167 AN: 152058 Hom.: 26573 Cov.: 32 AF XY: 0.569 AC XY: 42297 AN XY: 74308

African (AFR) AF: 0.787 AC: 32644 AN: 41486

American (AMR) AF: 0.488 AC: 7457 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2018 AN: 3470

East Asian (EAS) AF: 0.713 AC: 3673 AN: 5154

South Asian (SAS) AF: 0.540 AC: 2602 AN: 4820

European-Finnish (FIN) AF: 0.430 AC: 4543 AN: 10562

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32335 AN: 67980

Other (OTH) AF: 0.595 AC: 1258 AN: 2114

Alfa AF: 0.516 Hom.: 45062

Bravo AF: 0.590

Asia WGS AF: 0.601 AC: 2096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.76
PhyloP100		-0.61
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: rs7917983; hg19: chr10-114732882;