ENST00000484212.5:c.198+42197A>C

Variant names:

• chr7-116068511-T-G
• rs1464776
• ENST00000484212.5:c.198+42197A>C

Variant summary

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

The ENST00000484212.5(TFEC):​c.198+42197A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,378 control chromosomes in the GnomAD database, including 23,469 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 0.55 (23469 hom., cov: 31)
• Consequence: TFEC ENST00000484212.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFEC	ENST00000484212.5	TSL:2	c.198+42197A>C		intron	N/A	ENSP00000417432.1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 83812 AN: 151260 Hom.: 23442 Cov.: 31

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.554 AC: 83888 AN: 151378 Hom.: 23469 Cov.: 31 AF XY: 0.556 AC XY: 41109 AN XY: 73976

African (AFR) AF: 0.607 AC: 25100 AN: 41362

American (AMR) AF: 0.586 AC: 8884 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1899 AN: 3456

East Asian (EAS) AF: 0.735 AC: 3789 AN: 5156

South Asian (SAS) AF: 0.516 AC: 2489 AN: 4820

European-Finnish (FIN) AF: 0.459 AC: 4832 AN: 10534

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35060 AN: 67590

Other (OTH) AF: 0.580 AC: 1219 AN: 2100

Alfa AF: 0.510 Hom.: 9222

Bravo AF: 0.566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.57
DANN	Benign	0.68
PhyloP100		-0.41
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: rs1464776; hg19: chr7-115708565;