6-42236277-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001395490.1(TRERF1):c.2994G>A(p.Thr998=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,612,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000077 (0 hom.)
• Consequence: TRERF1 NM_001395490.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.61

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]

LOC105375061 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 6-42236277-C-T is Benign according to our data. Variant chr6-42236277-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.61 with no splicing effect.
• BS2: High AC in GnomAd at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRERF1	NM_001395490.1	c.2994G>A	p.Thr998=	synonymous_variant	16/18	ENST00000695948.1
LOC105375061	XR_001744122.2	n.538-139C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRERF1	ENST00000695948.1	c.2994G>A	p.Thr998=	synonymous_variant	16/18		NM_001395490.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000102 AC: 25 AN: 246298 Hom.: 0 AF XY: 0.000135 AC XY: 18 AN XY: 133184

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000552

Gnomad SAS exome AF: 0.000731

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000767 AC: 112 AN: 1460368 Hom.: 0 Cov.: 32 AF XY: 0.0000991 AC XY: 72 AN XY: 726374

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000722

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000396

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74494

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000567

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

TRERF1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	1.0
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs539205473; hg19: chr6-42204015; COSMIC: COSV61671135;