chr6-42299264-G-C

Variant names:

• chr6-42299264-G-C
• rs4714595
• NM_001395490.1:c.-259+1374C>G

Variant summary

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

The NM_001395490.1(TRERF1):​c.-259+1374C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 151,416 control chromosomes in the GnomAD database, including 3,122 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 0.18 (3122 hom., cov: 31)
• Consequence: TRERF1 NM_001395490.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRERF1	NM_001395490.1	c.-259+1374C>G		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.-259+1374C>G		intron_variant	Intron 4 of 17		NM_001395490.1	ENSP00000512293.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27498 AN: 151298 Hom.: 3126 Cov.: 31

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.182 AC: 27497 AN: 151416 Hom.: 3122 Cov.: 31 AF XY: 0.185 AC XY: 13704 AN XY: 73936

African (AFR) AF: 0.0430 AC: 1773 AN: 41226

American (AMR) AF: 0.268 AC: 4081 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3466

East Asian (EAS) AF: 0.319 AC: 1644 AN: 5160

South Asian (SAS) AF: 0.231 AC: 1100 AN: 4770

European-Finnish (FIN) AF: 0.238 AC: 2480 AN: 10402

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15402 AN: 67886

Other (OTH) AF: 0.187 AC: 391 AN: 2096

Alfa AF: 0.0940 Hom.: 138

Bravo AF: 0.178

Asia WGS AF: 0.255 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.65
PhyloP100		-0.67
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: rs4714595; hg19: chr6-42267002;