chr7-115968301-T-G

Variant names:

• chr7-115968301-T-G
• rs10248479
• ENST00000497829.1:n.13A>C

Variant summary

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

The ENST00000497829.1(TFEC):​n.13A>C variant causes a non coding transcript exon 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 ENST00000497829.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 5 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=-0.81).
• 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 rank	MANE	Protein	UniProt
TFEC	NM_012252.4	c.267+5869A>C		intron_variant	Intron 3 of 7	ENST00000265440.12	NP_036384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFEC	ENST00000265440.12	c.267+5869A>C		intron_variant	Intron 3 of 7	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

African (AFR) AF: 0.135 AC: 4054 AN: 30034

American (AMR) AF: 0.0749 AC: 2307 AN: 30808

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 4465 AN: 23554

East Asian (EAS) AF: 0.0177 AC: 626 AN: 35358

South Asian (SAS) AF: 0.138 AC: 10258 AN: 74322

European-Finnish (FIN) AF: 0.118 AC: 3815 AN: 32414

Middle Eastern (MID) AF: 0.178 AC: 974 AN: 5486

European-Non Finnish (NFE) AF: 0.130 AC: 138553 AN: 1065810

Other (OTH) AF: 0.129 AC: 7292 AN: 56376

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

African (AFR) AF: 0.137 AC: 5672 AN: 41456

American (AMR) AF: 0.102 AC: 1553 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 606 AN: 3458

East Asian (EAS) AF: 0.0266 AC: 137 AN: 5148

South Asian (SAS) AF: 0.123 AC: 595 AN: 4818

European-Finnish (FIN) AF: 0.122 AC: 1293 AN: 10598

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8926 AN: 67824

Other (OTH) AF: 0.146 AC: 307 AN: 2108

Alfa AF: 0.128 Hom.: 1988

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
PhyloP100		0.29
PromoterAI		0.028	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10248479; hg19: chr7-115608355;