rs7833986

Variant names:

• chr8-56187590-G-A
• rs7833986
• NM_002655.3:c.-321-8077C>T

Variant summary

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

The NM_002655.3(PLAG1):​c.-321-8077C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,116 control chromosomes in the GnomAD database, including 3,802 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 0.21 (3802 hom., cov: 32)
• Consequence: PLAG1 NM_002655.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 24 publications found

Genes affected

PLAG1 (HGNC:9045): (PLAG1 zinc finger) Pleomorphic adenoma gene 1 encodes a zinc finger protein with 2 putative nuclear localization signals. PLAG1, which is developmentally regulated, has been shown to be consistently rearranged in pleomorphic adenomas of the salivary glands. PLAG1 is activated by the reciprocal chromosomal translocations involving 8q12 in a subset of salivary gland pleomorphic adenomas. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PLAG1 Gene-Disease associations (from GenCC):

• silver-russell syndrome 4

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAG1	NM_002655.3	c.-321-8077C>T		intron_variant	Intron 1 of 4	ENST00000316981.8	NP_002646.2
PLAG1	NM_001114634.2	c.-216-16401C>T		intron_variant	Intron 1 of 3		NP_001108106.1
PLAG1	NM_001114635.2	c.-103-16401C>T		intron_variant	Intron 1 of 2		NP_001108107.1
PLAG1	XM_017013576.2	c.-449-8077C>T		intron_variant	Intron 1 of 5		XP_016869065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAG1	ENST00000316981.8	c.-321-8077C>T		intron_variant	Intron 1 of 4	1	NM_002655.3	ENSP00000325546.3
PLAG1	ENST00000429357.2	c.-216-16401C>T		intron_variant	Intron 1 of 3	1		ENSP00000416537.2
PLAG1	ENST00000423799.6	c.-103-16401C>T		intron_variant	Intron 1 of 2	2		ENSP00000404067.2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32273 AN: 151998 Hom.: 3781 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0731

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.213 AC: 32343 AN: 152116 Hom.: 3802 Cov.: 32 AF XY: 0.209 AC XY: 15508 AN XY: 74364

African (AFR) AF: 0.307 AC: 12708 AN: 41442

American (AMR) AF: 0.179 AC: 2735 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 969 AN: 3472

East Asian (EAS) AF: 0.0729 AC: 378 AN: 5186

South Asian (SAS) AF: 0.143 AC: 688 AN: 4828

European-Finnish (FIN) AF: 0.146 AC: 1545 AN: 10586

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12431 AN: 67996

Other (OTH) AF: 0.222 AC: 467 AN: 2106

Alfa AF: 0.193 Hom.: 13441

Bravo AF: 0.219

Asia WGS AF: 0.140 AC: 489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.037
DANN	Benign	0.35
PhyloP100		-1.3
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: rs7833986; hg19: chr8-57100149;