6-42227178-T-C

Position:

• chr6-42227178-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395490.1(TRERF1):​c.*1167A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,170 control chromosomes in the GnomAD database, including 25,097 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 0.55 (25097 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: TRERF1 NM_001395490.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRERF1	NM_001395490.1	c.*1167A>G		3_prime_UTR_variant	18/18	ENST00000695948.1	NP_001382419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRERF1	ENST00000695948.1	c.*1167A>G		3_prime_UTR_variant	18/18		NM_001395490.1	ENSP00000512293.1
TRERF1	ENST00000541110.5	c.*1167A>G		3_prime_UTR_variant	18/18	1		ENSP00000439689.1
TRERF1	ENST00000372922.8	c.*1167A>G		3_prime_UTR_variant	18/18	1		ENSP00000362013.4
TRERF1	ENST00000695966.1	c.*1167A>G		3_prime_UTR_variant	18/18			ENSP00000512292.1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84196 AN: 152048 Hom.: 25084 Cov.: 33

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.564

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.554 AC: 84241 AN: 152166 Hom.: 25097 Cov.: 33 AF XY: 0.563 AC XY: 41890 AN XY: 74388

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.836

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.562

Alfa AF: 0.613 Hom.: 34202

Bravo AF: 0.538

Asia WGS AF: 0.730 AC: 2534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.76

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: rs722269; hg19: chr6-42194916;