Variant chr1-150268830-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001077628.3(APH1A):c.-20C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,602,014 control chromosomes in the GnomAD database, including 13,362 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 0.10 ( 1093 hom., cov: 31)

Exomes 𝑓: 0.12 ( 12269 hom. )

Consequence

APH1A
NM_001077628.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.08

Variant links:

Genes affected

APH1A (HGNC:29509): (aph-1 homolog A, gamma-secretase subunit) This gene encodes a component of the gamma secretase complex that cleaves integral membrane proteins such as Notch receptors and beta-amyloid precursor protein. The gamma secretase complex contains this gene product, or the paralogous anterior pharynx defective 1 homolog B (APH1B), along with the presenilin, nicastrin, and presenilin enhancer-2 proteins. The precise function of this seven-transmembrane-domain protein is unknown though it is suspected of facilitating the association of nicastrin and presenilin in the gamma secretase complex as well as interacting with substrates of the gamma secretase complex prior to their proteolytic processing. Polymorphisms in a promoter region of this gene have been associated with an increased risk for developing sporadic Alzheimer's disease. Alternative splicing results in multiple protein-coding and non-protein-coding transcript variants. [provided by RefSeq, Aug 2011]

APH1A links:

C1orf54 (HGNC:26258): (chromosome 1 open reading frame 54) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

C1orf54 links:

APH1A (HGNC:):

APH1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APH1A	NM_001077628.3 linkuse as main transcript	c.-20C>A		5_prime_UTR_variant	1/7	ENST00000369109.8	NP_001071096.1	Q96BI3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APH1A	ENST00000369109.8 linkuse as main transcript	c.-20C>A		5_prime_UTR_variant	1/7	1	NM_001077628.3	ENSP00000358105.3		Q96BI3-1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15338

AN:

152056

Hom.:

1094

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0272

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.137

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.135

GnomAD3 exomes

AF:

0.136

AC:

30476

AN:

223536

Hom.:

2560

AF XY:

0.137

AC XY:

16762

AN XY:

122124

show subpopulations

Gnomad AFR exome

AF:

0.0227

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.360

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.123

AC:

179019

AN:

1449840

Hom.:

12269

Cov.:

AF XY:

0.124

AC XY:

89160

AN XY:

720306

show subpopulations

Gnomad4 AFR exome

AF:

0.0209

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.126

Gnomad4 EAS exome

AF:

0.334

Gnomad4 SAS exome

AF:

0.139

Gnomad4 FIN exome

AF:

0.119

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.134

GnomAD4 genome

AF:

0.101

AC:

15325

AN:

152174

Hom.:

1093

Cov.:

AF XY:

0.104

AC XY:

7716

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0271

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.351

Gnomad4 SAS

AF:

0.146

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.0929

Hom.:

356

Bravo

AF:

0.0993

Asia WGS

AF:

0.234

AC:

809

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.82

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.82

Position offset: -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