rs115005114

Variant names:

• chr3-129062280-C-T
• rs115005114
• NM_000174.5:c.*7C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000174.5(GP9):​c.*7C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00725 in 1,534,322 control chromosomes in the GnomAD database, including 301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (151 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (150 hom.)
• Consequence: GP9 NM_000174.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.250
• Publications: 1 publications found

Genes affected

GP9 (HGNC:4444): (glycoprotein IX platelet) This gene encodes a small membrane glycoprotein found on the surface of human platelets. It forms a 1-to-1 noncovalent complex with glycoprotein Ib, a platelet surface membrane glycoprotein complex that functions as a receptor for von Willebrand factor. The complete receptor complex includes noncovalent association of the alpha and beta subunits with the protein encoded by this gene and platelet glycoprotein V. Defects in this gene are a cause of Bernard-Soulier syndrome, also known as giant platelet disease. These patients have unusually large platelets and have a clinical bleeding tendency. [provided by RefSeq, Oct 2008]

GP9 Gene-Disease associations (from GenCC):

• Bernard-Soulier syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-129062280-C-T is Benign according to our data. Variant chr3-129062280-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000174.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP9	NM_000174.5	MANE Select	c.*7C>T		3_prime_UTR	Exon 3 of 3	NP_000165.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP9	ENST00000307395.5	TSL:1 MANE Select	c.*7C>T		3_prime_UTR	Exon 3 of 3	ENSP00000303942.4

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4093 AN: 152118 Hom.: 151 Cov.: 33

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00281

Gnomad OTH AF: 0.0292

GnomAD2 exomes AF: 0.00994 AC: 1397 AN: 140486 AF XY: 0.00837

Gnomad AFR exome AF: 0.0841

Gnomad AMR exome AF: 0.0117

Gnomad ASJ exome AF: 0.0418

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00327

Gnomad OTH exome AF: 0.0132

GnomAD4 exome AF: 0.00509 AC: 7030 AN: 1382086 Hom.: 150 Cov.: 29 AF XY: 0.00487 AC XY: 3315 AN XY: 681206

African (AFR) AF: 0.0800 AC: 2495 AN: 31182

American (AMR) AF: 0.0126 AC: 445 AN: 35186

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 1086 AN: 24962

East Asian (EAS) AF: 0.00 AC: 0 AN: 35670

South Asian (SAS) AF: 0.00112 AC: 88 AN: 78766

European-Finnish (FIN) AF: 0.0000211 AC: 1 AN: 47284

Middle Eastern (MID) AF: 0.0246 AC: 100 AN: 4060

European-Non Finnish (NFE) AF: 0.00199 AC: 2123 AN: 1067848

Other (OTH) AF: 0.0121 AC: 692 AN: 57128

GnomAD4 genome AF: 0.0269 AC: 4090 AN: 152236 Hom.: 151 Cov.: 33 AF XY: 0.0265 AC XY: 1974 AN XY: 74430

African (AFR) AF: 0.0808 AC: 3355 AN: 41526

American (AMR) AF: 0.0198 AC: 303 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00281 AC: 191 AN: 68006

Other (OTH) AF: 0.0289 AC: 61 AN: 2114

Alfa AF: 0.0114 Hom.: 15

Bravo AF: 0.0301

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Bernard Soulier syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.72
DANN	Benign	0.82
PhyloP100		0.25
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: rs115005114; hg19: chr3-128781123;