rs2587014

Positions:

• chr3-146540676-A-G

Variant summary

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

The NM_021105.3(PLSCR1):​c.-14+3791T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,046 control chromosomes in the GnomAD database, including 5,811 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 0.27 (5811 hom., cov: 32)
• Consequence: PLSCR1 NM_021105.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118

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]

PLSCR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLSCR1	NM_021105.3	c.-14+3791T>C		intron_variant		ENST00000342435.9	NP_066928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLSCR1	ENST00000342435.9	c.-14+3791T>C		intron_variant		1	NM_021105.3	ENSP00000345494.4

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41188 AN: 151928 Hom.: 5794 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.271 AC: 41245 AN: 152046 Hom.: 5811 Cov.: 32 AF XY: 0.271 AC XY: 20165 AN XY: 74324

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.255

Alfa AF: 0.254 Hom.: 2308

Bravo AF: 0.267

Asia WGS AF: 0.195 AC: 677 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.62

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: rs2587014; hg19: chr3-146258463;