Variant chr1-12793254-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000332296.7(PRAMEF1):c.27A>C(p.Leu9=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,549,876 control chromosomes in the GnomAD database, including 116,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9112 hom., cov: 30)

Exomes 𝑓: 0.36 ( 107666 hom. )

Consequence

PRAMEF1
ENST00000332296.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.14

Variant links:

Genes affected

PRAMEF1 (HGNC:28840): (PRAME family member 1) This gene is a member of the PRAME (preferentially expressed antigen of melanoma) gene family which is expressed in many cancers but may function in reproductive tissues during development. Alternative promoter usage generates two transcript variants, which encode different isoforms. [provided by RefSeq, Jun 2014]

PRAMEF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.07).

BP6

Variant 1-12793254-A-C is Benign according to our data. Variant chr1-12793254-A-C is described in ClinVar as [Benign]. Clinvar id is 769505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF1	NM_023013.4 linkuse as main transcript	c.27A>C	p.Leu9=	synonymous_variant	2/4	ENST00000332296.7	NP_075389.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRAMEF1	ENST00000332296.7 linkuse as main transcript	c.27A>C	p.Leu9=	synonymous_variant	2/4	1	NM_023013.4	ENSP00000332134	P1

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

48962

AN:

149664

Hom.:

9116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.432

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.495

Gnomad SAS

AF:

0.373

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.374

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.310

GnomAD3 exomes

AF:

0.367

AC:

85072

AN:

231860

Hom.:

18343

AF XY:

0.366

AC XY:

45989

AN XY:

125502

show subpopulations

Gnomad AFR exome

AF:

0.255

Gnomad AMR exome

AF:

0.402

Gnomad ASJ exome

AF:

0.259

Gnomad EAS exome

AF:

0.528

Gnomad SAS exome

AF:

0.373

Gnomad FIN exome

AF:

0.325

Gnomad NFE exome

AF:

0.362

Gnomad OTH exome

AF:

0.352

GnomAD4 exome

AF:

0.356

AC:

498441

AN:

1400096

Hom.:

107666

Cov.:

AF XY:

0.356

AC XY:

248005

AN XY:

697130

show subpopulations

Gnomad4 AFR exome

AF:

0.244

Gnomad4 AMR exome

AF:

0.382

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.505

Gnomad4 SAS exome

AF:

0.358

Gnomad4 FIN exome

AF:

0.323

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.356

GnomAD4 genome

AF:

0.327

AC:

48972

AN:

149780

Hom.:

9112

Cov.:

AF XY:

0.324

AC XY:

23663

AN XY:

73044

show subpopulations

Gnomad4 AFR

AF:

0.258

Gnomad4 AMR

AF:

0.321

Gnomad4 ASJ

AF:

0.251

Gnomad4 EAS

AF:

0.495

Gnomad4 SAS

AF:

0.372

Gnomad4 FIN

AF:

0.316

Gnomad4 NFE

AF:

0.359

Gnomad4 OTH

AF:

0.306

Alfa

AF:

0.278

Hom.:

1088

Bravo

AF:

0.332

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.73

DANN

Benign

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over