Genetic Variant NM_031283.3:c.34_42dupGGCGGCGGC (chr2-85133705-G-GGGCGGCGGC) – 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.34_42dupGGCGGCGGC(p.Gly12_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 0.000096 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000075 ( 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 14 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.34_42dupGGCGGCGGC	p.Gly12_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.34_42dupGGCGGCGGC	p.Gly12_Gly14dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000282111.3	Q9HCS4
TCF7L1	ENST00000922942.1		c.34_42dupGGCGGCGGC	p.Gly12_Gly14dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000593001.1
TCF7L1	ENST00000868102.1		c.34_42dupGGCGGCGGC	p.Gly12_Gly14dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000538161.1

Frequencies

GnomAD3 genomes

AF:

0.0000960

AC:

AN:

145814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000887

Gnomad EAS

AF:

0.00160

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000305

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000752

AC:

AN:

930944

Hom.:

Cov.:

AF XY:

0.0000732

AC XY:

AN XY:

437378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18368

American (AMR)

AF:

0.00

AC:

AN:

3854

Ashkenazi Jewish (ASJ)

AF:

0.000477

AC:

AN:

8384

East Asian (EAS)

AF:

0.0000892

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:

0.0000704

AC:

AN:

823756

Other (OTH)

AF:

0.000209

AC:

AN:

33456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

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:

0.0000959

AC:

AN:

145922

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

70970

show subpopulations

African (AFR)

AF:

0.0000246

AC:

AN:

40662

American (AMR)

AF:

0.00

AC:

AN:

14736

Ashkenazi Jewish (ASJ)

AF:

0.000887

AC:

AN:

3384

East Asian (EAS)

AF:

0.00160

AC:

AN:

4986

South Asian (SAS)

AF:

0.00

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000305

AC:

AN:

65656

Other (OTH)

AF:

0.00

AC:

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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