7-116008166-T-C

Variant names:

• chr7-116008166-T-C
• rs11764997
• NM_012252.4:c.-73+22467A>G

Variant summary

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

The NM_012252.4(TFEC):​c.-73+22467A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,004 control chromosomes in the GnomAD database, including 13,434 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 0.40 (13434 hom., cov: 32)
• Consequence: TFEC NM_012252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 1 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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFEC	NM_012252.4	c.-73+22467A>G		intron_variant	Intron 1 of 7	ENST00000265440.12	NP_036384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFEC	ENST00000265440.12	c.-73+22467A>G		intron_variant	Intron 1 of 7	1	NM_012252.4	ENSP00000265440.7
TFEC	ENST00000320239.11	c.-73+22467A>G		intron_variant	Intron 1 of 6	1		ENSP00000318676.7
TFEC	ENST00000484212.5	c.199-23653A>G		intron_variant	Intron 3 of 8	2		ENSP00000417432.1
TFEC	ENST00000393485.5	c.-73+22467A>G		intron_variant	Intron 1 of 5	2		ENSP00000377125.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61466 AN: 151886 Hom.: 13433 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.404 AC: 61482 AN: 152004 Hom.: 13434 Cov.: 32 AF XY: 0.402 AC XY: 29898 AN XY: 74292

African (AFR) AF: 0.245 AC: 10148 AN: 41474

American (AMR) AF: 0.369 AC: 5629 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1520 AN: 3472

East Asian (EAS) AF: 0.247 AC: 1275 AN: 5160

South Asian (SAS) AF: 0.448 AC: 2161 AN: 4822

European-Finnish (FIN) AF: 0.532 AC: 5612 AN: 10552

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.498 AC: 33833 AN: 67944

Other (OTH) AF: 0.402 AC: 848 AN: 2112

Alfa AF: 0.439 Hom.: 2613

Bravo AF: 0.387

Asia WGS AF: 0.310 AC: 1081 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.0
DANN	Benign	0.68
PhyloP100		0.079
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: rs11764997; hg19: chr7-115648220; COSMIC: COSV55401879;