dbSNP rs7574999: TCF7L1:c.525+264A>G (chr2-85283842-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031283.3(TCF7L1):c.525+264A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,088 control chromosomes in the GnomAD database, including 33,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33429 hom., cov: 31)

Consequence

TCF7L1
NM_031283.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.09

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 2-85283842-A-G is Benign according to our data. Variant chr2-85283842-A-G is described in ClinVar as [Benign]. Clinvar id is 1289588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L1	NM_031283.3 link	c.525+264A>G		intron_variant	Intron 4 of 11	ENST00000282111.4	NP_112573.1	Q9HCS4
TCF7L1	XM_006712109.3 link	c.525+264A>G		intron_variant	Intron 4 of 11		XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4 link	c.525+264A>G		intron_variant	Intron 4 of 11	1	NM_031283.3	ENSP00000282111.3		Q9HCS4
TCF7L1	ENST00000442813.1 link	c.75+264A>G		intron_variant	Intron 5 of 5	5		ENSP00000388984.1		C9JPE3

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

99715

AN:

151970

Hom.:

33387

Cov.:

show subpopulations

Gnomad AFR

AF:

0.785

Gnomad AMI

AF:

0.757

Gnomad AMR

AF:

0.616

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.440

Gnomad SAS

AF:

0.584

Gnomad FIN

AF:

0.506

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.627

Gnomad OTH

AF:

0.646

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

GnomAD4 genome

AF:

0.656

AC:

99809

AN:

152088

Hom.:

33429

Cov.:

AF XY:

0.647

AC XY:

48133

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.785

Gnomad4 AMR

AF:

0.616

Gnomad4 ASJ

AF:

0.722

Gnomad4 EAS

AF:

0.442

Gnomad4 SAS

AF:

0.583

Gnomad4 FIN

AF:

0.506

Gnomad4 NFE

AF:

0.627

Gnomad4 OTH

AF:

0.646

Alfa

AF:

0.646

Hom.:

6109

Bravo

AF:

0.672

Asia WGS

AF:

0.564

AC:

1958

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.12

DANN

Benign

0.32

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over