rs4714586

Variant names:

• chr6-42276892-G-A
• rs4714586
• NM_001395490.1:c.-258-7044C>T

Variant summary

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

The NM_001395490.1(TRERF1):​c.-258-7044C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,958 control chromosomes in the GnomAD database, including 14,971 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 0.44 (14971 hom., cov: 32)
• Consequence: TRERF1 NM_001395490.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 6 publications found

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]

TRERF1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRERF1	NM_001395490.1	c.-258-7044C>T		intron_variant	Intron 4 of 17	ENST00000695948.1	NP_001382419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRERF1	ENST00000695948.1	c.-258-7044C>T		intron_variant	Intron 4 of 17		NM_001395490.1	ENSP00000512293.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66309 AN: 151840 Hom.: 14937 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.437 AC: 66403 AN: 151958 Hom.: 14971 Cov.: 32 AF XY: 0.441 AC XY: 32769 AN XY: 74256

African (AFR) AF: 0.538 AC: 22289 AN: 41426

American (AMR) AF: 0.474 AC: 7236 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 854 AN: 3468

East Asian (EAS) AF: 0.456 AC: 2350 AN: 5156

South Asian (SAS) AF: 0.355 AC: 1714 AN: 4822

European-Finnish (FIN) AF: 0.462 AC: 4871 AN: 10552

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25858 AN: 67944

Other (OTH) AF: 0.409 AC: 862 AN: 2108

Alfa AF: 0.391 Hom.: 20336

Bravo AF: 0.444

Asia WGS AF: 0.453 AC: 1573 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.59
PhyloP100		-0.49
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: rs4714586; hg19: chr6-42244630;