ENST00000484212.5:c.-69+19263A>G

Variant names:

• chr7-116140527-T-C
• rs2402036
• ENST00000484212.5:c.-69+19263A>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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFEC	XM_011515963.2	c.-69+19263A>G		intron_variant	Intron 1 of 9		XP_011514265.1
TFEC	XM_011515964.3	c.-98+19263A>G		intron_variant	Intron 1 of 9		XP_011514266.1
TFEC	XM_011515965.3	c.-69+10017A>G		intron_variant	Intron 1 of 9		XP_011514267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFEC	ENST00000484212.5	c.-69+19263A>G		intron_variant	Intron 1 of 8	2		ENSP00000417432.1
TFEC	ENST00000465322.1	n.165+16775A>G		intron_variant	Intron 2 of 3	3
TFEC	ENST00000474337.5	n.106+19263A>G		intron_variant	Intron 1 of 4	3

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 v4.3

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

Other links and lift over

dbSNP: rs2402036; hg19: chr7-115780581;