Variant 14-73136423-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000557356.5(PSEN1):c.-161C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.056 in 152,976 control chromosomes in the GnomAD database, including 324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 324 hom., cov: 33)

Exomes 𝑓: 0.054 ( 0 hom. )

Consequence

PSEN1
ENST00000557356.5 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.71

Variant links:

Genes affected

PSEN1 (HGNC:9508): (presenilin 1) Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or in the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene, the full-length nature of only some have been determined. [provided by RefSeq, Aug 2008]

PSEN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 14-73136423-C-T is Benign according to our data. Variant chr14-73136423-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 369076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSEN1	XM_047431601.1 linkuse as main transcript	c.-161C>T		5_prime_UTR_variant	1/12
PSEN1	XM_047431602.1 linkuse as main transcript	c.-161C>T		5_prime_UTR_variant	1/12

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Appris	UniProt
PSEN1	ENST00000557356.5 linkuse as main transcript	c.-161C>T	5_prime_UTR_variant	1/5	4
PSEN1	ENST00000357710.8 linkuse as main transcript		upstream_gene_variant		1	A1	P49768-2
PSEN1	ENST00000555386.6 linkuse as main transcript		upstream_gene_variant		1		P49768-3

Frequencies

GnomAD3 genomes

AF:

0.0561

AC:

8534

AN:

152196

Hom.:

324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0416

Gnomad ASJ

AF:

0.0620

Gnomad EAS

AF:

0.00867

Gnomad SAS

AF:

0.0163

Gnomad FIN

AF:

0.0688

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0886

Gnomad OTH

AF:

0.0522

GnomAD4 exome

AF:

0.0544

AC:

AN:

662

Hom.:

Cov.:

AF XY:

0.0482

AC XY:

AN XY:

436

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0461

Gnomad4 NFE exome

AF:

0.0722

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.0560

AC:

8533

AN:

152314

Hom.:

324

Cov.:

AF XY:

0.0533

AC XY:

3968

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0162

Gnomad4 AMR

AF:

0.0415

Gnomad4 ASJ

AF:

0.0620

Gnomad4 EAS

AF:

0.00869

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.0688

Gnomad4 NFE

AF:

0.0886

Gnomad4 OTH

AF:

0.0517

Alfa

AF:

0.0738

Hom.:

137

Bravo

AF:

0.0532

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dilated Cardiomyopathy, Dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Pick disease;C0338451:Frontotemporal dementia;C1843013:Alzheimer disease 3;C3151038:Acne inversa, familial, 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Early-onset autosomal dominant Alzheimer disease

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.81

Splicing

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