Genetic Variant TRERF1:c.*1167A>G (chr6-42227178-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.181

Publications

14 publications found

Variant links:

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

TRERF1 links:

LOC105375061 (HGNC:):

LOC105375061 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TRERF1	NM_001395490.1 link	c.*1167A>G		3_prime_UTR_variant	Exon 18 of 18	ENST00000695948.1	NP_001382419.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRERF1	ENST00000695948.1 link	c.*1167A>G	3_prime_UTR_variant	Exon 18 of 18		NM_001395490.1	ENSP00000512293.1	A0A8Q3SI57
TRERF1	ENST00000541110.5 link	c.*1167A>G	3_prime_UTR_variant	Exon 18 of 18	1		ENSP00000439689.1	Q05GC8
TRERF1	ENST00000372922.8 link	c.*1167A>G	3_prime_UTR_variant	Exon 18 of 18	1		ENSP00000362013.4	Q96PN7-1
TRERF1	ENST00000695966.1 link	c.*1167A>G	3_prime_UTR_variant	Exon 18 of 18			ENSP00000512292.1	Q96PN7-1

Frequencies

GnomAD3 genomes

AF:

0.554

AC:

84196

AN:

152048

Hom.:

25084

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.554

AC:

84241

AN:

152166

Hom.:

25097

Cov.:

AF XY:

0.563

AC XY:

41890

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.316

AC:

13132

AN:

41502

American (AMR)

AF:

0.594

AC:

9076

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

1984

AN:

3472

East Asian (EAS)

AF:

0.836

AC:

4337

AN:

5186

South Asian (SAS)

AF:

0.745

AC:

3591

AN:

4822

European-Finnish (FIN)

AF:

0.714

AC:

7556

AN:

10586

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.628

AC:

42727

AN:

67992

Other (OTH)

AF:

0.562

AC:

1189

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1801

3602

5404

7205

9006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.595

Hom.:

54988

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

(source)

DANN

Benign

0.76

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over