Genetic Variant TCF7L1:p.Gly11_Gly14del (chr2-85133705-GGGCGGCGGCGGC-G) – 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.31_42delGGCGGCGGCGGC(p.Gly11_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 0.0000232 in 1,076,756 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

TCF7L1
NM_031283.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.50

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 17 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.31_42delGGCGGCGGCGGC	p.Gly11_Gly14del	conservative_inframe_deletion	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.31_42delGGCGGCGGCGGC	p.Gly11_Gly14del	conservative_inframe_deletion	Exon 1 of 12	ENSP00000282111.3	Q9HCS4
TCF7L1	ENST00000922942.1		c.31_42delGGCGGCGGCGGC	p.Gly11_Gly14del	conservative_inframe_deletion	Exon 1 of 12	ENSP00000593001.1
TCF7L1	ENST00000868102.1		c.31_42delGGCGGCGGCGGC	p.Gly11_Gly14del	conservative_inframe_deletion	Exon 1 of 12	ENSP00000538161.1

Frequencies

GnomAD3 genomes

AF:

0.000117

AC:

AN:

145814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000419

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000859

AC:

AN:

930942

Hom.:

AF XY:

0.00000457

AC XY:

AN XY:

437376

show subpopulations

African (AFR)

AF:

0.000381

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:

0.00

AC:

AN:

18060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11700

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2152

European-Non Finnish (NFE)

AF:

0.00000121

AC:

AN:

823754

Other (OTH)

AF:

0.00

AC:

AN:

33456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

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:

0.000117

AC:

AN:

145814

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

70850

show subpopulations

African (AFR)

AF:

0.000419

AC:

AN:

40544

American (AMR)

AF:

0.00

AC:

AN:

14718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3384

East Asian (EAS)

AF:

0.00

AC:

AN:

5002

South Asian (SAS)

AF:

0.00

AC:

AN:

4776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65666

Other (OTH)

AF:

0.00

AC:

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

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

2.5

Mutation Taster

=193/7

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-GGGC

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