chr2-85283842-A-G

Position:

• chr2-85283842-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000282111.4(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 ENST00000282111.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.09

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 -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/exons	MANE	Protein	UniProt
TCF7L1	NM_031283.3	c.525+264A>G		intron_variant		ENST00000282111.4	NP_112573.1
TCF7L1	XM_006712109.3	c.525+264A>G		intron_variant			XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4	c.525+264A>G		intron_variant		1	NM_031283.3	ENSP00000282111.3
TCF7L1	ENST00000442813.1	c.75+264A>G		intron_variant		5		ENSP00000388984.1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99715 AN: 151970 Hom.: 33387 Cov.: 31

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.: 31 AF XY: 0.647 AC XY: 48133 AN XY: 74340

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	0.12
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

Other links and lift over

dbSNP: rs7574999; hg19: chr2-85510965;