rs114126055

Variant names:

• chr6-42263347-C-A
• rs114126055
• NM_001395490.1:c.1857G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-42263347-C-A
• chr6-42263347-C-G
• chr6-42263347-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001395490.1(TRERF1):​c.1857G>T​(p.Ser619Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000448 in 1,612,962 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 0.0023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (3 hom.)
• Consequence: TRERF1 NM_001395490.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0900
• Publications: 2 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 6-42263347-C-A is Benign according to our data. Variant chr6-42263347-C-A is described in ClinVar as [Benign]. Clinvar id is 785171.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.09 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRERF1	NM_001395490.1	c.1857G>T	p.Ser619Ser	synonymous_variant	Exon 8 of 18	ENST00000695948.1	NP_001382419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRERF1	ENST00000695948.1	c.1857G>T	p.Ser619Ser	synonymous_variant	Exon 8 of 18		NM_001395490.1	ENSP00000512293.1

Frequencies

GnomAD3 genomes AF: 0.00235 AC: 357 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00827

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000640 AC: 160 AN: 249888 AF XY: 0.000555

Gnomad AFR exome AF: 0.00918

Gnomad AMR exome AF: 0.000237

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000251 AC: 366 AN: 1460618 Hom.: 3 Cov.: 32 AF XY: 0.000234 AC XY: 170 AN XY: 726574

African (AFR) AF: 0.00944 AC: 316 AN: 33472

American (AMR) AF: 0.000315 AC: 14 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111538

Other (OTH) AF: 0.000530 AC: 32 AN: 60358

GnomAD4 genome AF: 0.00234 AC: 356 AN: 152344 Hom.: 0 Cov.: 32 AF XY: 0.00231 AC XY: 172 AN XY: 74504

African (AFR) AF: 0.00823 AC: 342 AN: 41576

American (AMR) AF: 0.000523 AC: 8 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.00286

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	5.4
DANN	Benign	0.82
PhyloP100		-0.090
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs114126055; hg19: chr6-42231085; COSMIC: COSV100551470;