rs7240884

Positions:

• chr18-59901461-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021127.3(PMAIP1):​c.59-1186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,988 control chromosomes in the GnomAD database, including 25,529 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 0.55 (25529 hom., cov: 32)
• Consequence: PMAIP1 NM_021127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

Genes affected

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMAIP1	NM_021127.3	c.59-1186A>G		intron_variant		ENST00000316660.7	NP_066950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMAIP1	ENST00000316660.7	c.59-1186A>G		intron_variant		1	NM_021127.3	ENSP00000326119	P1
PMAIP1	ENST00000269518.9	c.209+883A>G		intron_variant		1		ENSP00000269518
PMAIP1	ENST00000590596.1	n.487+747A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83763 AN: 151870 Hom.: 25480 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.552 AC: 83866 AN: 151988 Hom.: 25529 Cov.: 32 AF XY: 0.553 AC XY: 41100 AN XY: 74284

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.486

Alfa AF: 0.430 Hom.: 19012

Bravo AF: 0.566

Asia WGS AF: 0.587 AC: 2038 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs7240884; hg19: chr18-57568693;