rs6785930

Variant names:

• chr3-151338828-G-A
• rs6785930
• NM_022788.5:c.18C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-151338828-G-A
• chr3-151338828-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_022788.5(P2RY12):​c.18C>T​(p.Asn6Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,610,536 control chromosomes in the GnomAD database, including 74,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5847 hom., cov: 31)
  • Exomes 𝑓: 0.31 (69141 hom.)
• Consequence: P2RY12 NM_022788.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.08
• Publications: 68 publications found

Genes affected

P2RY12 (HGNC:18124): (purinergic receptor P2Y12) The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is involved in platelet aggregation, and is a potential target for the treatment of thromboembolisms and other clotting disorders. Mutations in this gene are implicated in bleeding disorder, platelet type 8 (BDPLT8). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

MED12L Gene-Disease associations (from GenCC):

• Nizon-Isidor syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Illumina, Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 3-151338828-G-A is Benign according to our data. Variant chr3-151338828-G-A is described in ClinVar as Benign. ClinVar VariationId is 261632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022788.5. 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
	P2RY12	NM_022788.5	MANE Select	c.18C>T	p.Asn6Asn	synonymous	Exon 3 of 3	NP_073625.1	Q9H244
	MED12L	NM_001393769.1	MANE Select	c.2251-11231G>A		intron	N/A	NP_001380698.1	A0A8I5KX78
	P2RY12	NM_176876.3		c.18C>T	p.Asn6Asn	synonymous	Exon 2 of 2	NP_795345.1	Q9H244

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RY12	ENST00000302632.4	TSL:1 MANE Select	c.18C>T	p.Asn6Asn	synonymous	Exon 3 of 3	ENSP00000307259.4	Q9H244
	MED12L	ENST00000687756.1	MANE Select	c.2251-11231G>A		intron	N/A	ENSP00000508695.1	A0A8I5KX78
	MED12L	ENST00000474524.5	TSL:1	c.2146-11231G>A		intron	N/A	ENSP00000417235.1	Q86YW9-1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41154 AN: 151804 Hom.: 5848 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.278

GnomAD2 exomes AF: 0.295 AC: 73921 AN: 250832 AF XY: 0.296

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.322

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.228

Gnomad FIN exome AF: 0.369

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.305 AC: 445058 AN: 1458612 Hom.: 69141 Cov.: 39 AF XY: 0.306 AC XY: 221828 AN XY: 725744

African (AFR) AF: 0.175 AC: 5841 AN: 33432

American (AMR) AF: 0.320 AC: 14267 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 5169 AN: 26122

East Asian (EAS) AF: 0.240 AC: 9535 AN: 39680

South Asian (SAS) AF: 0.296 AC: 25548 AN: 86188

European-Finnish (FIN) AF: 0.368 AC: 19667 AN: 53380

Middle Eastern (MID) AF: 0.271 AC: 1559 AN: 5762

European-Non Finnish (NFE) AF: 0.312 AC: 345965 AN: 1109100

Other (OTH) AF: 0.290 AC: 17507 AN: 60308

GnomAD4 genome AF: 0.271 AC: 41170 AN: 151924 Hom.: 5847 Cov.: 31 AF XY: 0.273 AC XY: 20291 AN XY: 74228

African (AFR) AF: 0.184 AC: 7619 AN: 41432

American (AMR) AF: 0.295 AC: 4500 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3466

East Asian (EAS) AF: 0.222 AC: 1143 AN: 5160

South Asian (SAS) AF: 0.302 AC: 1448 AN: 4802

European-Finnish (FIN) AF: 0.366 AC: 3859 AN: 10554

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

European-Non Finnish (NFE) AF: 0.310 AC: 21045 AN: 67948

Other (OTH) AF: 0.274 AC: 577 AN: 2104

Alfa AF: 0.287 Hom.: 13478

Bravo AF: 0.259

Asia WGS AF: 0.245 AC: 852 AN: 3478

EpiCase AF: 0.300

EpiControl AF: 0.296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.9
DANN	Benign	0.69
PhyloP100		1.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6785930; hg19: chr3-151056616; COSMIC: COSV99851706; COSMIC: COSV99851706;