6-42246553-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001395490.1(TRERF1):c.2657-9T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,591,362 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (38 hom.)
• Consequence: TRERF1 NM_001395490.1 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.07170
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.73

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 6-42246553-A-C is Benign according to our data. Variant chr6-42246553-A-C is described in ClinVar as [Benign]. Clinvar id is 779911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00263 (401/152320) while in subpopulation EAS AF= 0.022 (114/5188). AF 95% confidence interval is 0.0187. There are 8 homozygotes in gnomad4. There are 201 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 399 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRERF1	NM_001395490.1	c.2657-9T>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000695948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRERF1	ENST00000695948.1	c.2657-9T>G		splice_polypyrimidine_tract_variant, intron_variant			NM_001395490.1

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 399 AN: 152202 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00610 AC: 1411 AN: 231484 Hom.: 30 AF XY: 0.00460 AC XY: 577 AN XY: 125346

Gnomad AFR exome AF: 0.000899

Gnomad AMR exome AF: 0.0353

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0201

Gnomad SAS exome AF: 0.000549

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000644

Gnomad OTH exome AF: 0.00545

GnomAD4 exome AF: 0.00132 AC: 1902 AN: 1439042 Hom.: 38 Cov.: 27 AF XY: 0.00110 AC XY: 791 AN XY: 715862

Gnomad4 AFR exome AF: 0.000615

Gnomad4 AMR exome AF: 0.0310

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0105

Gnomad4 SAS exome AF: 0.000574

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000227

Gnomad4 OTH exome AF: 0.00259

GnomAD4 genome AF: 0.00263 AC: 401 AN: 152320 Hom.: 8 Cov.: 32 AF XY: 0.00270 AC XY: 201 AN XY: 74482

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0220

Gnomad4 SAS AF: 0.000827

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.000333 Hom.: 0

Bravo AF: 0.00423

Asia WGS AF: 0.0130 AC: 46 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

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	14
Dann	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.072
dbscSNV1_RF	Benign	0.33
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: rs117301162; hg19: chr6-42214291;