2-85283654-A-G

Variant names:

• chr2-85283654-A-G
• rs7574856
• NM_031283.3:c.525+76A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031283.3(TCF7L1):​c.525+76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 1,494,956 control chromosomes in the GnomAD database, including 190,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24269 hom., cov: 32)
  • Exomes 𝑓: 0.50 (166251 hom.)
• Consequence: TCF7L1 NM_031283.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.59
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-85283654-A-G is Benign according to our data. Variant chr2-85283654-A-G is described in ClinVar as Benign. ClinVar VariationId is 1277108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 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.525+76A>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.525+76A>G		intron	N/A	ENSP00000282111.3	Q9HCS4
	TCF7L1	ENST00000922942.1		c.525+76A>G		intron	N/A	ENSP00000593001.1
	TCF7L1	ENST00000868102.1		c.525+76A>G		intron	N/A	ENSP00000538161.1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84126 AN: 151954 Hom.: 24230 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.531

GnomAD4 exome AF: 0.496 AC: 665812 AN: 1342884 Hom.: 166251 AF XY: 0.496 AC XY: 334595 AN XY: 674042

African (AFR) AF: 0.748 AC: 23287 AN: 31130

American (AMR) AF: 0.520 AC: 23115 AN: 44460

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 12797 AN: 25376

East Asian (EAS) AF: 0.455 AC: 17748 AN: 38976

South Asian (SAS) AF: 0.546 AC: 45868 AN: 83962

European-Finnish (FIN) AF: 0.428 AC: 22107 AN: 51708

Middle Eastern (MID) AF: 0.578 AC: 3154 AN: 5456

European-Non Finnish (NFE) AF: 0.486 AC: 488902 AN: 1005308

Other (OTH) AF: 0.510 AC: 28834 AN: 56508

GnomAD4 genome AF: 0.554 AC: 84220 AN: 152072 Hom.: 24269 Cov.: 32 AF XY: 0.547 AC XY: 40670 AN XY: 74320

African (AFR) AF: 0.739 AC: 30644 AN: 41476

American (AMR) AF: 0.517 AC: 7913 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1776 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2240 AN: 5168

South Asian (SAS) AF: 0.539 AC: 2592 AN: 4808

European-Finnish (FIN) AF: 0.416 AC: 4403 AN: 10578

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32914 AN: 67964

Other (OTH) AF: 0.531 AC: 1119 AN: 2106

Alfa AF: 0.511 Hom.: 4695

Bravo AF: 0.570

Asia WGS AF: 0.532 AC: 1849 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.014
DANN	Benign	0.34
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7574856; hg19: chr2-85510777; COSMIC: COSV56397081;