Variant rs1061770 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_012392.4(PEF1):c.804T>C(p.Ile268=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 1,612,968 control chromosomes in the GnomAD database, including 229,577 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 0.42 ( 16240 hom., cov: 33)

Exomes 𝑓: 0.53 ( 213337 hom. )

Consequence

PEF1
NM_012392.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.201

Variant links:

Genes affected

PEF1 (HGNC:30009): (penta-EF-hand domain containing 1) This gene encodes a calcium-binding protein belonging to the penta-EF-hand protein family. The encoded protein has been shown to form a heterodimer with the programmed cell death 6 gene product and may modulate its function in Ca(2+) signaling. Alternative splicing results in multiple transcript variants and a pseudogene has been identified on chromosome 1.[provided by RefSeq, May 2010]

PEF1 links:

HCRTR1 (HGNC:4848): (hypocretin receptor 1) The protein encoded by this gene is a G-protein coupled receptor involved in the regulation of feeding behavior. The encoded protein selectively binds the hypothalamic neuropeptide orexin A. A related gene (HCRTR2) encodes a G-protein coupled receptor that binds orexin A and orexin B. [provided by RefSeq, Jan 2009]

HCRTR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP7

Synonymous conserved (PhyloP=-0.201 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEF1	NM_012392.4 linkuse as main transcript	c.804T>C	p.Ile268=	synonymous_variant	5/5	ENST00000373703.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PEF1	ENST00000373703.5 linkuse as main transcript	c.804T>C	p.Ile268=	synonymous_variant	5/5	1	NM_012392.4	P1
HCRTR1	ENST00000373705.1 linkuse as main transcript	c.1088-1772A>G		intron_variant		1
PEF1	ENST00000461006.5 linkuse as main transcript	n.408T>C		non_coding_transcript_exon_variant	4/4	5
PEF1	ENST00000478502.5 linkuse as main transcript	n.535T>C		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64367

AN:

151996

Hom.:

16239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.561

Gnomad AMR

AF:

0.467

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.538

Gnomad FIN

AF:

0.566

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.457

GnomAD3 exomes

AF:

0.499

AC:

125285

AN:

250984

Hom.:

33396

AF XY:

0.513

AC XY:

69598

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.489

Gnomad ASJ exome

AF:

0.575

Gnomad EAS exome

AF:

0.263

Gnomad SAS exome

AF:

0.554

Gnomad FIN exome

AF:

0.564

Gnomad NFE exome

AF:

0.557

Gnomad OTH exome

AF:

0.516

GnomAD4 exome

AF:

0.534

AC:

779439

AN:

1460854

Hom.:

213337

Cov.:

AF XY:

0.537

AC XY:

389946

AN XY:

726730

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.486

Gnomad4 ASJ exome

AF:

0.573

Gnomad4 EAS exome

AF:

0.243

Gnomad4 SAS exome

AF:

0.559

Gnomad4 FIN exome

AF:

0.562

Gnomad4 NFE exome

AF:

0.556

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.423

AC:

64379

AN:

152114

Hom.:

16240

Cov.:

AF XY:

0.425

AC XY:

31559

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.145

Gnomad4 AMR

AF:

0.468

Gnomad4 ASJ

AF:

0.569

Gnomad4 EAS

AF:

0.251

Gnomad4 SAS

AF:

0.538

Gnomad4 FIN

AF:

0.566

Gnomad4 NFE

AF:

0.555

Gnomad4 OTH

AF:

0.452

Alfa

AF:

0.496

Hom.:

8767

Bravo

AF:

0.404

Asia WGS

AF:

0.374

AC:

1300

AN:

3478

EpiCase

AF:

0.557

EpiControl

AF:

0.559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.8

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over