rs6798232

Positions:

• chr3-142650997-G-A

Variant summary

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

The NM_001145319.2(PLS1):​c.-36-13205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,938 control chromosomes in the GnomAD database, including 30,090 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 0.62 (30090 hom., cov: 30)
• Consequence: PLS1 NM_001145319.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

Genes affected

PLS1 (HGNC:9090): (plastin 1) Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. The protein encoded by this gene is a third distinct plastin isoform, which is specifically expressed at high levels in the small intestine. Alternatively spliced transcript variants varying in the 5' UTR, but encoding the same protein, have been found for this gene. A pseudogene of this gene is found on chromosome 11.[provided by RefSeq, Feb 2010]

LOC105374136 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLS1	NM_001145319.2	c.-36-13205G>A		intron_variant		ENST00000457734.7	NP_001138791.1
LOC105374136	XR_001740938.2	n.253+5561C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLS1	ENST00000457734.7	c.-36-13205G>A		intron_variant		2	NM_001145319.2	ENSP00000387890	P1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94825 AN: 151820 Hom.: 30059 Cov.: 30

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.625 AC: 94899 AN: 151938 Hom.: 30090 Cov.: 30 AF XY: 0.621 AC XY: 46099 AN XY: 74268

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.615

Alfa AF: 0.617 Hom.: 6171

Bravo AF: 0.613

Asia WGS AF: 0.471 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.34

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: rs6798232; hg19: chr3-142369839;