7-116140527-T-C

Variant names:

• chr7-116140527-T-C
• rs2402036
• ENST00000871199.1:c.-339+10017A>G

Variant summary

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

The ENST00000484212.5(TFEC):​c.-69+19263A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,190 control chromosomes in the GnomAD database, including 4,858 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 0.23 (4858 hom., cov: 32)
• Consequence: TFEC ENST00000484212.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703
• Publications: 7 publications found

Genes affected

TFEC (HGNC:11754): (transcription factor EC) This gene encodes a member of the micropthalmia (MiT) family of basic helix-loop-helix leucine zipper transcription factors. MiT transcription factors regulate the expression of target genes by binding to E-box recognition sequences as homo- or heterodimers, and play roles in multiple cellular processes including survival, growth and differentiation. The encoded protein is a transcriptional activator of the nonmuscle myosin II heavy chain-A gene, and may also co-regulate target genes in osteoclasts as a heterodimer with micropthalmia-associated transcription factor. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000484212.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFEC	ENST00000871199.1		c.-339+10017A>G		intron	N/A	ENSP00000541258.1
	TFEC	ENST00000871198.1		c.-339+19263A>G		intron	N/A	ENSP00000541257.1
	TFEC	ENST00000484212.5	TSL:2	c.-69+19263A>G		intron	N/A	ENSP00000417432.1	B7Z757

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34411 AN: 152072 Hom.: 4856 Cov.: 32

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.226 AC: 34430 AN: 152190 Hom.: 4858 Cov.: 32 AF XY: 0.227 AC XY: 16897 AN XY: 74400

African (AFR) AF: 0.0580 AC: 2412 AN: 41562

American (AMR) AF: 0.339 AC: 5177 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3470

East Asian (EAS) AF: 0.182 AC: 943 AN: 5184

South Asian (SAS) AF: 0.241 AC: 1163 AN: 4828

European-Finnish (FIN) AF: 0.266 AC: 2810 AN: 10568

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20273 AN: 67980

Other (OTH) AF: 0.226 AC: 477 AN: 2110

Alfa AF: 0.276 Hom.: 4800

Bravo AF: 0.224

Asia WGS AF: 0.170 AC: 593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2402036;

hg19: chr7-115780581;