Genetic Variant TCF7L1:p.Gly14dup (chr2-85133705-G-GGGC) – 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.40_42dupGGC(p.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 0.00014 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00013 ( 0 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 21 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.40_42dupGGC	p.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.40_42dupGGC	p.Gly14dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000282111.3	Q9HCS4
TCF7L1	ENST00000922942.1		c.40_42dupGGC	p.Gly14dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000593001.1
TCF7L1	ENST00000868102.1		c.40_42dupGGC	p.Gly14dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000538161.1

Frequencies

GnomAD3 genomes

AF:

0.000144

AC:

AN:

145814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000740

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000400

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.000118

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000137

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

520

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000126

AC:

117

AN:

930918

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

437368

show subpopulations

African (AFR)

AF:

0.0000544

AC:

AN:

18368

American (AMR)

AF:

0.00

AC:

AN:

3854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8384

East Asian (EAS)

AF:

0.00

AC:

AN:

11214

South Asian (SAS)

AF:

0.000277

AC:

AN:

18060

European-Finnish (FIN)

AF:

0.0000855

AC:

AN:

11700

Middle Eastern (MID)

AF:

0.000929

AC:

AN:

2152

European-Non Finnish (NFE)

AF:

0.000129

AC:

106

AN:

823730

Other (OTH)

AF:

0.0000598

AC:

AN:

33456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000144

AC:

AN:

145814

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

AN XY:

70850

show subpopulations

African (AFR)

AF:

0.0000740

AC:

AN:

40544

American (AMR)

AF:

0.000340

AC:

AN:

14718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3384

East Asian (EAS)

AF:

0.000400

AC:

AN:

5002

South Asian (SAS)

AF:

0.000209

AC:

AN:

4776

European-Finnish (FIN)

AF:

0.000118

AC:

AN:

8492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.000137

AC:

AN:

65666

Other (OTH)

AF:

0.00

AC:

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

542

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-GGGCGGCGGCGGCGGCGGC

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