7-115968301-T-G

Position:

• chr7-115968301-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001244583.2(TFEC):​c.-51A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,505,996 control chromosomes in the GnomAD database, including 12,754 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 0.13 (1336 hom., cov: 32)
  • Exomes 𝑓: 0.13 (11418 hom.)
• Consequence: TFEC NM_001244583.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289

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]

TFEC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFEC	NM_012252.4	c.267+5869A>C		intron_variant		ENST00000265440.12	NP_036384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFEC	ENST00000265440.12	c.267+5869A>C		intron_variant		1	NM_012252.4	ENSP00000265440.7

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19327 AN: 151716 Hom.: 1338 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.127 AC: 172344 AN: 1354162 Hom.: 11418 Cov.: 30 AF XY: 0.128 AC XY: 85692 AN XY: 667744

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.0749

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.0177

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.127 AC: 19333 AN: 151834 Hom.: 1336 Cov.: 32 AF XY: 0.126 AC XY: 9347 AN XY: 74214

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.0266

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.146

Alfa AF: 0.128 Hom.: 1692

Bravo AF: 0.124

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.8
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs10248479; hg19: chr7-115608355;