5-134123023-T-C

Variant names:

• chr5-134123023-T-C
• rs152404
• NM_003202.5:c.441+6990T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003202.5(TCF7):​c.441+6990T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,170 control chromosomes in the GnomAD database, including 7,791 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (7791 hom., cov: 32)
• Consequence: TCF7 NM_003202.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 5 publications found

Genes affected

TCF7 (HGNC:11639): (transcription factor 7) This gene encodes a member of the T-cell factor/lymphoid enhancer-binding factor family of high mobility group (HMG) box transcriptional activators. This gene is expressed predominantly in T-cells and plays a critical role in natural killer cell and innate lymphoid cell development. The encoded protein forms a complex with beta-catenin and activates transcription through a Wnt/beta-catenin signaling pathway. Mice with a knockout of this gene are viable and fertile, but display a block in T-lymphocyte differentiation. Alternative splicing results in multiple transcript variants. Naturally-occurring isoforms lacking the N-terminal beta-catenin interaction domain may act as dominant negative regulators of Wnt signaling. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003202.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7	NM_003202.5	MANE Select	c.441+6990T>C		intron	N/A	NP_003193.2
	TCF7	NM_001346425.2		c.441+6990T>C		intron	N/A	NP_001333354.1
	TCF7	NM_001346450.2		c.96+6990T>C		intron	N/A	NP_001333379.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7	ENST00000342854.10	TSL:1 MANE Select	c.441+6990T>C		intron	N/A	ENSP00000340347.5
	TCF7	ENST00000395023.5	TSL:1	c.96+6990T>C		intron	N/A	ENSP00000378469.1
	TCF7	ENST00000518915.5	TSL:1	c.96+6990T>C		intron	N/A	ENSP00000430179.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42703 AN: 152052 Hom.: 7763 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.281 AC: 42787 AN: 152170 Hom.: 7791 Cov.: 32 AF XY: 0.289 AC XY: 21504 AN XY: 74384

African (AFR) AF: 0.489 AC: 20296 AN: 41512

American (AMR) AF: 0.379 AC: 5793 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3472

East Asian (EAS) AF: 0.437 AC: 2259 AN: 5164

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4814

European-Finnish (FIN) AF: 0.216 AC: 2292 AN: 10610

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9686 AN: 68000

Other (OTH) AF: 0.277 AC: 585 AN: 2112

Alfa AF: 0.224 Hom.: 2248

Bravo AF: 0.307

Asia WGS AF: 0.326 AC: 1131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.4
DANN	Benign	0.36
PhyloP100		-0.24
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: rs152404; hg19: chr5-133458714;