Genetic Variant TCF7L1:p.Gly13_Gly14dup (chr2-85133705-G-GGGCGGC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_031283.3(TCF7L1):c.37_42dupGGCGGC(p.Gly13_Gly14dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0075 ( 12 hom., cov: 0)

Exomes 𝑓: 0.0092 ( 35 hom. )

Consequence

TCF7L1
NM_031283.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0880

Publications

5 publications found

Variant links:

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

TCF7L1 links:

ENSG00000300535 (HGNC:):

ENSG00000300535 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 1101 AD gene.

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.37_42dupGGCGGC	p.Gly13_Gly14dup	conservative_inframe_insertion	Exon 1 of 12	NP_112573.1	Q9HCS4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCF7L1	ENST00000282111.4	TSL:1 MANE Select	c.37_42dupGGCGGC	p.Gly13_Gly14dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000282111.3	Q9HCS4
TCF7L1	ENST00000922942.1		c.37_42dupGGCGGC	p.Gly13_Gly14dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000593001.1
TCF7L1	ENST00000868102.1		c.37_42dupGGCGGC	p.Gly13_Gly14dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000538161.1

Frequencies

GnomAD3 genomes

AF:

0.00755

AC:

1101

AN:

145806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00885

Gnomad AMR

AF:

0.00156

Gnomad ASJ

AF:

0.00207

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000628

Gnomad FIN

AF:

0.0411

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00979

Gnomad OTH

AF:

0.00248

GnomAD2 exomes

AF:

0.00385

AC:

AN:

520

AF XY:

0.00333

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00422

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00925

AC:

8608

AN:

930778

Hom.:

Cov.:

AF XY:

0.00913

AC XY:

3991

AN XY:

437296

show subpopulations

African (AFR)

AF:

0.000871

AC:

AN:

18368

American (AMR)

AF:

0.00156

AC:

AN:

3854

Ashkenazi Jewish (ASJ)

AF:

0.00107

AC:

AN:

8384

East Asian (EAS)

AF:

0.00

AC:

AN:

11214

South Asian (SAS)

AF:

0.000609

AC:

AN:

18060

European-Finnish (FIN)

AF:

0.0124

AC:

145

AN:

11656

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2152

European-Non Finnish (NFE)

AF:

0.00999

AC:

8225

AN:

823636

Other (OTH)

AF:

0.00586

AC:

196

AN:

33454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

373

747

1120

1494

1867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

416

832

1248

1664

2080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00755

AC:

1101

AN:

145914

Hom.:

Cov.:

AF XY:

0.00872

AC XY:

619

AN XY:

70968

show subpopulations

African (AFR)

AF:

0.00155

AC:

AN:

40662

American (AMR)

AF:

0.00156

AC:

AN:

14736

Ashkenazi Jewish (ASJ)

AF:

0.00207

AC:

AN:

3384

East Asian (EAS)

AF:

0.00

AC:

AN:

4986

South Asian (SAS)

AF:

0.000629

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.0411

AC:

349

AN:

8488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00979

AC:

643

AN:

65652

Other (OTH)

AF:

0.00245

AC:

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

109

163

218

272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00712

Hom.:

542

Bravo

AF:

0.00472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.088

Mutation Taster

=82/18

polymorphism

(source)

Splicing

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

Publications

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2-85133705-GGGCGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGCGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over