dbSNP rs151822: TCF7:c.441+4237G>A (chr5-134120270-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003202.5(TCF7):c.441+4237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,054 control chromosomes in the GnomAD database, including 33,040 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.64 ( 33040 hom., cov: 32)

Consequence

TCF7
NM_003202.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.239

Publications

11 publications found

Variant links:

Genes affected

TCF7 (HGNC:11639): (transcription factor 7) This gene encodes a member of the T-cell factor/lymphoid enhancer-binding factor family of high mobility group (HMG) box transcriptional activators. This gene is expressed predominantly in T-cells and plays a critical role in natural killer cell and innate lymphoid cell development. The encoded protein forms a complex with beta-catenin and activates transcription through a Wnt/beta-catenin signaling pathway. Mice with a knockout of this gene are viable and fertile, but display a block in T-lymphocyte differentiation. Alternative splicing results in multiple transcript variants. Naturally-occurring isoforms lacking the N-terminal beta-catenin interaction domain may act as dominant negative regulators of Wnt signaling. [provided by RefSeq, Oct 2016]

TCF7 links:

ENSG00000307917 (HGNC:):

ENSG00000307917 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003202.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TCF7	NM_003202.5	MANE Select	c.441+4237G>A	intron	N/A	NP_003193.2
TCF7	NM_001346425.2		c.441+4237G>A	intron	N/A	NP_001333354.1
TCF7	NM_001346450.2		c.96+4237G>A	intron	N/A	NP_001333379.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TCF7	ENST00000342854.10	TSL:1 MANE Select	c.441+4237G>A	intron	N/A	ENSP00000340347.5
TCF7	ENST00000395023.5	TSL:1	c.96+4237G>A	intron	N/A	ENSP00000378469.1
TCF7	ENST00000518915.5	TSL:1	c.96+4237G>A	intron	N/A	ENSP00000430179.1

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97822

AN:

151938

Hom.:

33040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.920

Gnomad AMR

AF:

0.562

Gnomad ASJ

AF:

0.756

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.594

Gnomad FIN

AF:

0.694

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.775

Gnomad OTH

AF:

0.655

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.644

AC:

97851

AN:

152054

Hom.:

33040

Cov.:

AF XY:

0.635

AC XY:

47165

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.462

AC:

19137

AN:

41436

American (AMR)

AF:

0.561

AC:

8573

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.756

AC:

2626

AN:

3472

East Asian (EAS)

AF:

0.433

AC:

2230

AN:

5154

South Asian (SAS)

AF:

0.594

AC:

2869

AN:

4830

European-Finnish (FIN)

AF:

0.694

AC:

7344

AN:

10582

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.775

AC:

52657

AN:

67972

Other (OTH)

AF:

0.654

AC:

1382

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1637

3274

4912

6549

8186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

778

1556

2334

3112

3890

<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:

0.736

Hom.:

20980

Bravo

AF:

0.623

Asia WGS

AF:

0.533

AC:

1854

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.3

(source)

DANN

Benign

0.92

PhyloP100

-0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over