5-134116844-C-T

Variant names:

• chr5-134116844-C-T
• rs244692
• NM_003202.5:c.441+811C>T

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+811C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 152,340 control chromosomes in the GnomAD database, including 63,984 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 0.92 (63984 hom., cov: 35)
• Consequence: TCF7 NM_003202.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.922 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7	NM_003202.5	MANE Select	c.441+811C>T		intron	N/A	NP_003193.2
	TCF7	NM_001346425.2		c.441+811C>T		intron	N/A	NP_001333354.1
	TCF7	NM_001346450.2		c.96+811C>T		intron	N/A	NP_001333379.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7	ENST00000342854.10	TSL:1 MANE Select	c.441+811C>T		intron	N/A	ENSP00000340347.5	P36402-5
	TCF7	ENST00000395023.5	TSL:1	c.96+811C>T		intron	N/A	ENSP00000378469.1	P36402-6
	TCF7	ENST00000518915.5	TSL:1	c.96+811C>T		intron	N/A	ENSP00000430179.1	P36402-2

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139476 AN: 152222 Hom.: 63928 Cov.: 35

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.926

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

GnomAD4 genome AF: 0.916 AC: 139593 AN: 152340 Hom.: 63984 Cov.: 35 AF XY: 0.915 AC XY: 68152 AN XY: 74490

African (AFR) AF: 0.917 AC: 38141 AN: 41590

American (AMR) AF: 0.935 AC: 14312 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3251 AN: 3472

East Asian (EAS) AF: 0.905 AC: 4696 AN: 5188

South Asian (SAS) AF: 0.836 AC: 4034 AN: 4826

European-Finnish (FIN) AF: 0.910 AC: 9661 AN: 10614

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62380 AN: 68030

Other (OTH) AF: 0.926 AC: 1956 AN: 2112

Alfa AF: 0.920 Hom.: 100742

Bravo AF: 0.922

Asia WGS AF: 0.878 AC: 3053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.61
PhyloP100		-0.51
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: rs244692; hg19: chr5-133452535;