ENST00000369102.5:c.-150+969G>C

Variant names:

• chr1-150269789-G-C
• rs3754048
• ENST00000369102.5:c.-150+969G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000369102.5(C1orf54):​c.-150+969G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,038 control chromosomes in the GnomAD database, including 9,847 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 0.35 (9847 hom., cov: 32)
• Consequence: C1orf54 ENST00000369102.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 9 publications found

Genes affected

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

LOC124904414 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369102.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf54	ENST00000369102.5	TSL:5	c.-150+969G>C		intron	N/A	ENSP00000358098.1
	APH1A	ENST00000493092.1	TSL:3	n.-209C>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52924 AN: 151920 Hom.: 9833 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.348 AC: 52973 AN: 152038 Hom.: 9847 Cov.: 32 AF XY: 0.354 AC XY: 26285 AN XY: 74340

African (AFR) AF: 0.410 AC: 16967 AN: 41426

American (AMR) AF: 0.423 AC: 6457 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3466

East Asian (EAS) AF: 0.598 AC: 3096 AN: 5176

South Asian (SAS) AF: 0.468 AC: 2258 AN: 4826

European-Finnish (FIN) AF: 0.282 AC: 2986 AN: 10576

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19307 AN: 67972

Other (OTH) AF: 0.361 AC: 762 AN: 2110

Alfa AF: 0.159 Hom.: 284

Bravo AF: 0.359

Asia WGS AF: 0.496 AC: 1724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.82
DANN	Benign	0.56
PhyloP100		-1.6
PromoterAI		0.0018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3754048; hg19: chr1-150242189;