7-116099511-C-T

Variant names:

• chr7-116099511-C-T
• rs12673240
• ENST00000484212.5:c.198+11197G>A

Variant summary

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

The ENST00000484212.5(TFEC):​c.198+11197G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,990 control chromosomes in the GnomAD database, including 10,109 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 0.36 (10109 hom., cov: 32)
• Consequence: TFEC ENST00000484212.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFEC	XM_011515963.2	c.198+11197G>A		intron_variant	Intron 3 of 9		XP_011514265.1
TFEC	XM_011515964.3	c.198+11197G>A		intron_variant	Intron 3 of 9		XP_011514266.1
TFEC	XM_011515965.3	c.198+11197G>A		intron_variant	Intron 3 of 9		XP_011514267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFEC	ENST00000484212.5	c.198+11197G>A		intron_variant	Intron 3 of 8	2		ENSP00000417432.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54086 AN: 151872 Hom.: 10086 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.356 AC: 54156 AN: 151990 Hom.: 10109 Cov.: 32 AF XY: 0.363 AC XY: 26926 AN XY: 74256

African (AFR) AF: 0.387 AC: 16065 AN: 41460

American (AMR) AF: 0.425 AC: 6492 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3468

East Asian (EAS) AF: 0.689 AC: 3551 AN: 5156

South Asian (SAS) AF: 0.408 AC: 1965 AN: 4814

European-Finnish (FIN) AF: 0.308 AC: 3241 AN: 10536

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20799 AN: 67976

Other (OTH) AF: 0.354 AC: 747 AN: 2110

Alfa AF: 0.335 Hom.: 1404

Bravo AF: 0.364

Asia WGS AF: 0.551 AC: 1907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.24
DANN	Benign	0.61
PhyloP100		-1.3
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: rs12673240; hg19: chr7-115739565;