18-59899607-G-T

Variant names:

• chr18-59899607-G-T
• rs4558496
• ENST00000848866.1:n.218+409C>A

Variant summary

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

The ENST00000848866.1(ENSG00000310295):​n.218+409C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 151,914 control chromosomes in the GnomAD database, including 52,657 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 0.83 (52657 hom., cov: 29)
• Consequence: ENSG00000310295 ENST00000848866.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• Publications: 7 publications found

Genes affected

ENSG00000310295 (HGNC:):

PMAIP1 (HGNC:9108): (phorbol-12-myristate-13-acetate-induced protein 1) This gene belongs to a pro-apoptotic subfamily within the BCL-2 protein family, referred to as the BCL-2 homology domain 3 (BH3)-only subfamily, which determine whether a cell commits to apoptosis. In response to death-inducing stimuli, BH3-only members inhibit the anti-apoptotic BCL-2 family members, which under steady-state conditions keep the multi-BH domain proteins BAX and BAK, in an inactive state. [provided by RefSeq, Aug 2020]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000848866.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000310295	ENST00000848866.1		n.218+409C>A		intron	N/A
	PMAIP1	ENST00000919087.1		c.-239G>T		upstream_gene	N/A	ENSP00000589146.1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126248 AN: 151800 Hom.: 52613 Cov.: 29

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.832 AC: 126346 AN: 151914 Hom.: 52657 Cov.: 29 AF XY: 0.834 AC XY: 61921 AN XY: 74262

African (AFR) AF: 0.845 AC: 34976 AN: 41392

American (AMR) AF: 0.846 AC: 12916 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2678 AN: 3468

East Asian (EAS) AF: 0.957 AC: 4939 AN: 5160

South Asian (SAS) AF: 0.912 AC: 4385 AN: 4810

European-Finnish (FIN) AF: 0.835 AC: 8831 AN: 10582

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.811 AC: 55073 AN: 67920

Other (OTH) AF: 0.843 AC: 1776 AN: 2108

Alfa AF: 0.823 Hom.: 35470

Bravo AF: 0.833

Asia WGS AF: 0.920 AC: 3197 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.91
DANN	Benign	0.69
PhyloP100		-0.63
PromoterAI		-0.13	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4558496; hg19: chr18-57566839;