chr2-85283302-G-A

Variant names:

• chr2-85283302-G-A
• rs7601117
• NM_031283.3:c.442-193G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_031283.3(TCF7L1):​c.442-193G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,042 control chromosomes in the GnomAD database, including 7,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (7607 hom., cov: 30)
• Consequence: TCF7L1 NM_031283.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.911
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-85283302-G-A is Benign according to our data. Variant chr2-85283302-G-A is described in ClinVar as Benign. ClinVar VariationId is 1259370.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

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.442-193G>A		intron	N/A	NP_112573.1	Q9HCS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L1	ENST00000282111.4	TSL:1 MANE Select	c.442-193G>A		intron	N/A	ENSP00000282111.3	Q9HCS4
	TCF7L1	ENST00000922942.1		c.442-193G>A		intron	N/A	ENSP00000593001.1
	TCF7L1	ENST00000868102.1		c.442-193G>A		intron	N/A	ENSP00000538161.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44375 AN: 150924 Hom.: 7607 Cov.: 30

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.294 AC: 44388 AN: 151042 Hom.: 7607 Cov.: 30 AF XY: 0.290 AC XY: 21361 AN XY: 73762

African (AFR) AF: 0.109 AC: 4463 AN: 40788

American (AMR) AF: 0.272 AC: 4124 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1526 AN: 3462

East Asian (EAS) AF: 0.275 AC: 1412 AN: 5140

South Asian (SAS) AF: 0.299 AC: 1428 AN: 4770

European-Finnish (FIN) AF: 0.332 AC: 3495 AN: 10520

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26824 AN: 67878

Other (OTH) AF: 0.311 AC: 651 AN: 2094

Alfa AF: 0.359 Hom.: 17990

Bravo AF: 0.282

Asia WGS AF: 0.262 AC: 909 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.80
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7601117; hg19: chr2-85510425;