rs10248479

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-115968301-T-A
• chr7-115968301-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000497829.1(TFEC):​n.13A>T 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 0.0000059 in 1,355,028 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000059 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFEC	NM_012252.4	c.267+5869A>T		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>T		intron_variant	Intron 3 of 7	1	NM_012252.4	ENSP00000265440.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000590 AC: 8 AN: 1355028 Hom.: 0 Cov.: 30 AF XY: 0.00000599 AC XY: 4 AN XY: 668172

African (AFR) AF: 0.00 AC: 0 AN: 30050

American (AMR) AF: 0.00 AC: 0 AN: 30838

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23582

East Asian (EAS) AF: 0.00 AC: 0 AN: 35364

South Asian (SAS) AF: 0.00 AC: 0 AN: 74426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5492

European-Non Finnish (NFE) AF: 0.00000750 AC: 8 AN: 1066432

Other (OTH) AF: 0.00 AC: 0 AN: 56414

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1988

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.67
PhyloP100		0.29
PromoterAI		-0.0072	Neutral

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;