2-85283277-A-G

Position:

• chr2-85283277-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_031283.3(TCF7L1):​c.442-218A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 123,874 control chromosomes in the GnomAD database, including 8,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (8002 hom., cov: 28)
• Consequence: TCF7L1 NM_031283.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.689

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-85283277-A-G is Benign according to our data. Variant chr2-85283277-A-G is described in ClinVar as [Benign]. Clinvar id is 1283343.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L1	NM_031283.3	c.442-218A>G		intron_variant		ENST00000282111.4	NP_112573.1
TCF7L1	XM_006712109.3	c.442-218A>G		intron_variant			XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4	c.442-218A>G		intron_variant		1	NM_031283.3	ENSP00000282111	P1
TCF7L1	ENST00000442813.1	c.-9-218A>G		intron_variant		5		ENSP00000388984

Frequencies

GnomAD3 genomes AF: 0.379 AC: 46866 AN: 123800 Hom.: 7997 Cov.: 28

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.435

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.379 AC: 46896 AN: 123874 Hom.: 8002 Cov.: 28 AF XY: 0.372 AC XY: 22556 AN XY: 60612

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.372

Alfa AF: 0.338 Hom.: 986

Bravo AF: 0.303

Asia WGS AF: 0.271 AC: 939 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs34644194; hg19: chr2-85510400;