6-42236244-G-A

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.3027C>T(p.Pro1009=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000665 in 1,608,148 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (3 hom.)
• Consequence: TRERF1 NM_001395490.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.135

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=-0.63).
• BP6: Variant 6-42236244-G-A is Benign according to our data. Variant chr6-42236244-G-A is described in ClinVar as [Benign]. Clinvar id is 773327.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.135 with no splicing effect.
• BS2: High AC in GnomAd at 359 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRERF1	NM_001395490.1	c.3027C>T	p.Pro1009=	synonymous_variant	16/18	ENST00000695948.1
LOC105375061	XR_001744122.2	n.538-172G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRERF1	ENST00000695948.1	c.3027C>T	p.Pro1009=	synonymous_variant	16/18		NM_001395490.1

Frequencies

GnomAD3 genomes AF: 0.00236 AC: 359 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00671

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000957 AC: 234 AN: 244490 Hom.: 0 AF XY: 0.000794 AC XY: 105 AN XY: 132312

Gnomad AFR exome AF: 0.00585

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00220

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000673

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000551

Gnomad OTH exome AF: 0.00202

GnomAD4 exome AF: 0.000486 AC: 708 AN: 1455822 Hom.: 3 Cov.: 32 AF XY: 0.000479 AC XY: 347 AN XY: 724324

Gnomad4 AFR exome AF: 0.00672

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.00203

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000175

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000219

Gnomad4 OTH exome AF: 0.00133

GnomAD4 genome AF: 0.00237 AC: 361 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.00224 AC XY: 167 AN XY: 74490

Gnomad4 AFR AF: 0.00676

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00168 Hom.: 0

Bravo AF: 0.00284

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	5.6
Dann	Benign	0.67

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: rs78813717; hg19: chr6-42203982;