2-85133705-GGGCGGCGGCGGCGGC-GGGCGGCGGCGGC

Variant names:

• chr2-85133705-GGGC-G
• rs566806913
• NM_031283.3:c.40_42delGGC

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_031283.3(TCF7L1):​c.40_42delGGC​(p.Gly14del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,073,848 control chromosomes in the GnomAD database, including 92,149 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.44 (14475 hom., cov: 0)
  • Exomes 𝑓: 0.41 (77674 hom.)
• Consequence: TCF7L1 NM_031283.3 conservative_inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.0880
• Publications: 5 publications found

Genes affected

TCF7L1 (HGNC:11640): (transcription factor 7 like 1) This gene encodes a member of the T cell factor/lymphoid enhancer factor family of transcription factors. These transcription factors are activated by beta catenin, mediate the Wnt signaling pathway and are antagonized by the transforming growth factor beta signaling pathway. The encoded protein contains a high mobility group-box DNA binding domain and participates in the regulation of cell cycle genes and cellular senescence. [provided by RefSeq, Nov 2010]

TCF7L1 Gene-Disease associations (from GenCC):

• combined pituitary hormone deficiencies, genetic form

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ENSG00000300535 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 2-85133705-GGGC-G is Benign according to our data. Variant chr2-85133705-GGGC-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1299932.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031283.3. 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
	TCF7L1	NM_031283.3	MANE Select	c.40_42delGGC	p.Gly14del	conservative_inframe_deletion	Exon 1 of 12	NP_112573.1	Q9HCS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L1	ENST00000282111.4	TSL:1 MANE Select	c.40_42delGGC	p.Gly14del	conservative_inframe_deletion	Exon 1 of 12	ENSP00000282111.3	Q9HCS4
	TCF7L1	ENST00000922942.1		c.40_42delGGC	p.Gly14del	conservative_inframe_deletion	Exon 1 of 12	ENSP00000593001.1
	TCF7L1	ENST00000868102.1		c.40_42delGGC	p.Gly14del	conservative_inframe_deletion	Exon 1 of 12	ENSP00000538161.1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 63569 AN: 145690 Hom.: 14441 Cov.: 0

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.390

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.400

GnomAD2 exomes AF: 0.454 AC: 236 AN: 520 AF XY: 0.423

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad FIN exome AF: 0.533

Gnomad NFE exome AF: 0.445

Gnomad OTH exome AF: 0.300

GnomAD4 exome AF: 0.412 AC: 382737 AN: 928050 Hom.: 77674 AF XY: 0.411 AC XY: 179196 AN XY: 435986

African (AFR) AF: 0.557 AC: 10203 AN: 18332

American (AMR) AF: 0.415 AC: 1592 AN: 3840

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 3441 AN: 8342

East Asian (EAS) AF: 0.269 AC: 2980 AN: 11098

South Asian (SAS) AF: 0.327 AC: 5886 AN: 17994

European-Finnish (FIN) AF: 0.581 AC: 6777 AN: 11656

Middle Eastern (MID) AF: 0.322 AC: 689 AN: 2142

European-Non Finnish (NFE) AF: 0.412 AC: 337990 AN: 821326

Other (OTH) AF: 0.396 AC: 13179 AN: 33320

GnomAD4 genome AF: 0.437 AC: 63645 AN: 145798 Hom.: 14475 Cov.: 0 AF XY: 0.437 AC XY: 30962 AN XY: 70914

African (AFR) AF: 0.539 AC: 21887 AN: 40634

American (AMR) AF: 0.348 AC: 5119 AN: 14726

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1290 AN: 3382

East Asian (EAS) AF: 0.199 AC: 989 AN: 4980

South Asian (SAS) AF: 0.321 AC: 1529 AN: 4762

European-Finnish (FIN) AF: 0.509 AC: 4320 AN: 8480

Middle Eastern (MID) AF: 0.399 AC: 115 AN: 288

European-Non Finnish (NFE) AF: 0.412 AC: 27035 AN: 65600

Other (OTH) AF: 0.398 AC: 814 AN: 2044

Alfa AF: 0.238 Hom.: 542

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.088
Mutation Taster		=79/21	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: rs566806913; hg19: chr2-85360828; COSMIC: COSV56401914; COSMIC: COSV56401914;