rs4711716

Positions:

• chr6-42299485-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395490.1(TRERF1):​c.-259+1153T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,188 control chromosomes in the GnomAD database, including 1,680 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 0.14 (1680 hom., cov: 32)
• Consequence: TRERF1 NM_001395490.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171

Genes affected

TRERF1 (HGNC:18273): (transcriptional regulating factor 1) This gene encodes a zinc-finger transcriptional regulating protein which interacts with CBP/p300 to regulate the human gene CYP11A1. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRERF1	NM_001395490.1	c.-259+1153T>C		intron_variant		ENST00000695948.1	NP_001382419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRERF1	ENST00000695948.1	c.-259+1153T>C		intron_variant			NM_001395490.1	ENSP00000512293

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20561 AN: 152070 Hom.: 1672 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.0977

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.135 AC: 20602 AN: 152188 Hom.: 1680 Cov.: 32 AF XY: 0.138 AC XY: 10254 AN XY: 74424

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0893

Gnomad4 EAS AF: 0.0978

Gnomad4 SAS AF: 0.0995

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.0896

Gnomad4 OTH AF: 0.117

Alfa AF: 0.103 Hom.: 534

Bravo AF: 0.139

Asia WGS AF: 0.116 AC: 405 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs4711716; hg19: chr6-42267223;