Variant rs3025786 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000021.4(PSEN1):c.770-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 1,426,226 control chromosomes in the GnomAD database, including 1,655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 138 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1517 hom. )

Consequence

PSEN1
NM_000021.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.18

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:

PSEN1 (HGNC:):

PSEN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 14-73198010-T-C is Benign according to our data. Variant chr14-73198010-T-C is described in ClinVar as [Benign]. Clinvar id is 1280880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-73198010-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSEN1	NM_000021.4 linkuse as main transcript	c.770-21T>C		intron_variant		ENST00000324501.10	NP_000012.1	P49768-1A0A024R6A3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSEN1	ENST00000324501.10 linkuse as main transcript	c.770-21T>C		intron_variant		1	NM_000021.4	ENSP00000326366.5		P49768-1

Frequencies

GnomAD3 genomes

AF:

0.0357

AC:

5427

AN:

152198

Hom.:

140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00907

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.0414

Gnomad ASJ

AF:

0.0354

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0126

Gnomad FIN

AF:

0.0266

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0547

Gnomad OTH

AF:

0.0512

GnomAD3 exomes

AF:

0.0353

AC:

8593

AN:

243740

Hom.:

217

AF XY:

0.0360

AC XY:

4742

AN XY:

131776

show subpopulations

Gnomad AFR exome

AF:

0.00704

Gnomad AMR exome

AF:

0.0275

Gnomad ASJ exome

AF:

0.0310

Gnomad EAS exome

AF:

0.000386

Gnomad SAS exome

AF:

0.0118

Gnomad FIN exome

AF:

0.0282

Gnomad NFE exome

AF:

0.0552

Gnomad OTH exome

AF:

0.0410

GnomAD4 exome

AF:

0.0447

AC:

56986

AN:

1273910

Hom.:

1517

Cov.:

AF XY:

0.0443

AC XY:

28468

AN XY:

643116

show subpopulations

Gnomad4 AFR exome

AF:

0.00759

Gnomad4 AMR exome

AF:

0.0297

Gnomad4 ASJ exome

AF:

0.0316

Gnomad4 EAS exome

AF:

0.000180

Gnomad4 SAS exome

AF:

0.0127

Gnomad4 FIN exome

AF:

0.0288

Gnomad4 NFE exome

AF:

0.0524

Gnomad4 OTH exome

AF:

0.0433

GnomAD4 genome

AF:

0.0356

AC:

5420

AN:

152316

Hom.:

138

Cov.:

AF XY:

0.0342

AC XY:

2544

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00904

Gnomad4 AMR

AF:

0.0413

Gnomad4 ASJ

AF:

0.0354

Gnomad4 EAS

AF:

0.000770

Gnomad4 SAS

AF:

0.0126

Gnomad4 FIN

AF:

0.0266

Gnomad4 NFE

AF:

0.0546

Gnomad4 OTH

AF:

0.0497

Alfa

AF:

0.0457

Hom.:

Bravo

AF:

0.0367

Asia WGS

AF:

0.0110

AC:

AN:

3478

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	GeneDx	Mar 12, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.4

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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