chr2-85283277-A-G

Variant names:

• chr2-85283277-A-G
• rs34644194
• NM_031283.3:c.442-218A>G

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.442-218A>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
• Publications: 2 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]

TCF7L1 Gene-Disease associations (from GenCC):

• combined pituitary hormone deficiencies, genetic form

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.442-218A>G		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.442-218A>G		intron	N/A	ENSP00000282111.3	Q9HCS4
	TCF7L1	ENST00000922942.1		c.442-218A>G		intron	N/A	ENSP00000593001.1
	TCF7L1	ENST00000868102.1		c.442-218A>G		intron	N/A	ENSP00000538161.1

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

African (AFR) AF: 0.324 AC: 6924 AN: 21360

American (AMR) AF: 0.333 AC: 4206 AN: 12628

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1518 AN: 3300

East Asian (EAS) AF: 0.318 AC: 1413 AN: 4448

South Asian (SAS) AF: 0.357 AC: 1437 AN: 4024

European-Finnish (FIN) AF: 0.347 AC: 3475 AN: 10014

Middle Eastern (MID) AF: 0.443 AC: 109 AN: 246

European-Non Finnish (NFE) AF: 0.411 AC: 26791 AN: 65178

Other (OTH) AF: 0.372 AC: 671 AN: 1804

Alfa AF: 0.338 Hom.: 986

Bravo AF: 0.303

Asia WGS AF: 0.271 AC: 939 AN: 3474

ClinVar

ClinVar submissions

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	-0.91
CADD	Benign	0.41
DANN	Benign	0.18
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34644194; hg19: chr2-85510400;