rs2587028

Positions:

• chr3-146525174-C-T

Variant summary

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

The NM_021105.3(PLSCR1):​c.355+431G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,218 control chromosomes in the GnomAD database, including 1,109 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 0.11 (1109 hom., cov: 33)
• Consequence: PLSCR1 NM_021105.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520

Genes affected

PLSCR1 (HGNC:9092): (phospholipid scramblase 1) This gene encodes a phospholipid scramblase family member. The encoded protein is involved in disruption of the asymmetrical distribution of phospholipids between the inner and outer leaflets of the plasma membrane, resulting in externalization of phosphatidylserine. This cell membrane disruption plays an important role in the blood coagulation cascade as well as macrophage clearing of apoptotic cells. The encoded protein has additionally been implicated in gene regulation and interferon-induced antiviral responses. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLSCR1	NM_021105.3	c.355+431G>A		intron_variant		ENST00000342435.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLSCR1	ENST00000342435.9	c.355+431G>A		intron_variant		1	NM_021105.3	P2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16955 AN: 152100 Hom.: 1109 Cov.: 33

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0975

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.111 AC: 16961 AN: 152218 Hom.: 1109 Cov.: 33 AF XY: 0.114 AC XY: 8453 AN XY: 74414

Gnomad4 AFR AF: 0.0489

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0975

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.120

Alfa AF: 0.130 Hom.: 1614

Bravo AF: 0.110

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.8
DANN	Benign	0.77

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: rs2587028; hg19: chr3-146242961;