6-46704623-G-A

Variant names:

• chr6-46704623-G-A
• rs202232077
• NM_005084.4:c.1263C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_005084.4(PLA2G7):​c.1263C>T​(p.Asn421Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,584,112 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: PLA2G7 NM_005084.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.341
• Publications: 0 publications found

Genes affected

PLA2G7 (HGNC:9040): (phospholipase A2 group VII) The protein encoded by this gene is a secreted enzyme that catalyzes the degradation of platelet-activating factor to biologically inactive products. Defects in this gene are a cause of platelet-activating factor acetylhydrolase deficiency. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-46704623-G-A is Benign according to our data. Variant chr6-46704623-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3385175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.341 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4	c.1263C>T	p.Asn421Asn	synonymous_variant	Exon 12 of 12	ENST00000274793.12	NP_005075.3
PLA2G7	NM_001168357.2	c.1263C>T	p.Asn421Asn	synonymous_variant	Exon 12 of 12		NP_001161829.1
PLA2G7	XM_005249408.5	c.1263C>T	p.Asn421Asn	synonymous_variant	Exon 12 of 12		XP_005249465.1
PLA2G7	XM_047419359.1	c.1128C>T	p.Asn376Asn	synonymous_variant	Exon 11 of 11		XP_047275315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G7	ENST00000274793.12	c.1263C>T	p.Asn421Asn	synonymous_variant	Exon 12 of 12	1	NM_005084.4	ENSP00000274793.7
PLA2G7	ENST00000537365.1	c.1263C>T	p.Asn421Asn	synonymous_variant	Exon 12 of 12	1		ENSP00000445666.1

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152064 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000195 AC: 49 AN: 251052 AF XY: 0.000228

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000667

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000144 AC: 206 AN: 1432048 Hom.: 1 Cov.: 27 AF XY: 0.000167 AC XY: 119 AN XY: 714456

African (AFR) AF: 0.000454 AC: 15 AN: 33006

American (AMR) AF: 0.000628 AC: 28 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25936

East Asian (EAS) AF: 0.00 AC: 0 AN: 39524

South Asian (SAS) AF: 0.00 AC: 0 AN: 85724

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53376

Middle Eastern (MID) AF: 0.000700 AC: 4 AN: 5716

European-Non Finnish (NFE) AF: 0.000130 AC: 141 AN: 1084786

Other (OTH) AF: 0.000286 AC: 17 AN: 59378

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152064 Hom.: 0 Cov.: 31 AF XY: 0.000188 AC XY: 14 AN XY: 74272

African (AFR) AF: 0.000314 AC: 13 AN: 41412

American (AMR) AF: 0.000459 AC: 7 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67998

Other (OTH) AF: 0.00144 AC: 3 AN: 2086

Alfa AF: 0.000201 Hom.: 0

Bravo AF: 0.000317

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 21, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.39
PhyloP100		-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

Other links and lift over

dbSNP: rs202232077; hg19: chr6-46672360;