chr3-146531132-T-C

Variant names:

• chr3-146531132-T-C
• rs2587025
• NM_021105.3:c.95-2301A>G

Variant summary

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

The NM_001406033.1(PLSCR1):​c.131-2301A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,040 control chromosomes in the GnomAD database, including 12,408 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 0.40 (12408 hom., cov: 32)
• Consequence: PLSCR1 NM_001406033.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193
• Publications: 0 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001406033.1. 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
	PLSCR1	NM_021105.3	MANE Select	c.95-2301A>G		intron	N/A	NP_066928.1
	PLSCR1	NM_001406033.1		c.131-2301A>G		intron	N/A	NP_001392962.1
	PLSCR1	NM_001406034.1		c.95-2301A>G		intron	N/A	NP_001392963.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLSCR1	ENST00000342435.9	TSL:1 MANE Select	c.95-2301A>G		intron	N/A	ENSP00000345494.4
	PLSCR1	ENST00000469266.1	TSL:1	n.369-2301A>G		intron	N/A
	PLSCR1	ENST00000493432.5	TSL:1	n.94+2338A>G		intron	N/A	ENSP00000419680.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60882 AN: 151922 Hom.: 12379 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.401 AC: 60965 AN: 152040 Hom.: 12408 Cov.: 32 AF XY: 0.397 AC XY: 29501 AN XY: 74314

African (AFR) AF: 0.463 AC: 19195 AN: 41468

American (AMR) AF: 0.413 AC: 6316 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1176 AN: 3472

East Asian (EAS) AF: 0.197 AC: 1018 AN: 5168

South Asian (SAS) AF: 0.299 AC: 1437 AN: 4810

European-Finnish (FIN) AF: 0.363 AC: 3837 AN: 10578

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26638 AN: 67954

Other (OTH) AF: 0.383 AC: 808 AN: 2110

Alfa AF: 0.367 Hom.: 5121

Bravo AF: 0.408

Asia WGS AF: 0.287 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.9
DANN	Benign	0.77
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2587025; hg19: chr3-146248919;