rs189534942

chr19-55032557-G-Achr19-55032557-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001083899.2(GP6):c.35-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,613,340 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0084 (6 hom., cov: 33)
  • Exomes 𝑓: 0.011 (104 hom.)
• Consequence: GP6 NM_001083899.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.20

Genes affected

GP6 (HGNC:14388): (glycoprotein VI platelet) This gene encodes a platelet membrane glycoprotein of the immunoglobulin superfamily. The encoded protein is a receptor for collagen and plays a critical role in collagen-induced platelet aggregation and thrombus formation. The encoded protein forms a complex with the Fc receptor gamma-chain that initiates the platelet activation signaling cascade upon collagen binding. Mutations in this gene are a cause of platelet-type bleeding disorder-11 (BDPLT11). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

GP6-AS1 (HGNC:55305): (GP6 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-55032557-G-A is Benign according to our data. Variant chr19-55032557-G-A is described in ClinVar as [Benign]. Clinvar id is 257417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00838 (1277/152362) while in subpopulation NFE AF= 0.0124 (845/68022). AF 95% confidence interval is 0.0117. There are 6 homozygotes in gnomad4. There are 634 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GP6	NM_001083899.2	c.35-19C>T		intron_variant		ENST00000310373.7
GP6-AS1	XR_001754012.3	n.122-10243G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GP6	ENST00000310373.7	c.35-19C>T		intron_variant		1	NM_001083899.2
GP6-AS1	ENST00000593060.5	n.156-10243G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00839 AC: 1277 AN: 152244 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00914 AC: 2220 AN: 243012 Hom.: 14 AF XY: 0.00927 AC XY: 1226 AN XY: 132284

Gnomad AFR exome AF: 0.00153

Gnomad AMR exome AF: 0.00370

Gnomad ASJ exome AF: 0.00537

Gnomad EAS exome AF: 0.0000559

Gnomad SAS exome AF: 0.00713

Gnomad FIN exome AF: 0.0209

Gnomad NFE exome AF: 0.0120

Gnomad OTH exome AF: 0.00931

GnomAD4 exome AF: 0.0110 AC: 16045 AN: 1460978 Hom.: 104 Cov.: 34 AF XY: 0.0111 AC XY: 8048 AN XY: 726722

Gnomad4 AFR exome AF: 0.00158

Gnomad4 AMR exome AF: 0.00361

Gnomad4 ASJ exome AF: 0.00677

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00700

Gnomad4 FIN exome AF: 0.0220

Gnomad4 NFE exome AF: 0.0119

Gnomad4 OTH exome AF: 0.00948

GnomAD4 genome AF: 0.00838 AC: 1277 AN: 152362 Hom.: 6 Cov.: 33 AF XY: 0.00851 AC XY: 634 AN XY: 74504

Gnomad4 AFR AF: 0.00190

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00600

Gnomad4 FIN AF: 0.0218

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.0104 Hom.: 3

Bravo AF: 0.00679

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.1
Dann	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs189534942; hg19: chr19-55543925;