19-55013969-G-A

Position:

• chr19-55013969-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000310373.7(GP6):​c.*113C>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 0.05 in 427,944 control chromosomes in the GnomAD database, including 1,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (624 hom., cov: 32)
  • Exomes 𝑓: 0.041 (467 hom.)
• Consequence: GP6 ENST00000310373.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.347

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=-0.62).
• BP6: Variant 19-55013969-G-A is Benign according to our data. Variant chr19-55013969-G-A is described in ClinVar as [Benign]. Clinvar id is 1223991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GP6	NM_001083899.2	c.*113C>T		3_prime_UTR_variant	8/8	ENST00000310373.7	NP_001077368.2
GP6-AS1	XR_001754012.3	n.121+7505G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7	c.*113C>T		3_prime_UTR_variant	8/8	1	NM_001083899.2	ENSP00000308782
GP6-AS1	ENST00000593060.5	n.155+7505G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0657 AC: 9984 AN: 152060 Hom.: 620 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0871

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.0657

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0196

Gnomad OTH AF: 0.0488

GnomAD4 exome AF: 0.0413 AC: 11393 AN: 275766 Hom.: 467 Cov.: 0 AF XY: 0.0418 AC XY: 6439 AN XY: 154000

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.0898

Gnomad4 ASJ exome AF: 0.0128

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.0584

Gnomad4 FIN exome AF: 0.0130

Gnomad4 NFE exome AF: 0.0199

Gnomad4 OTH exome AF: 0.0371

GnomAD4 genome AF: 0.0658 AC: 10011 AN: 152178 Hom.: 624 Cov.: 32 AF XY: 0.0655 AC XY: 4874 AN XY: 74410

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0871

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.0655

Gnomad4 FIN AF: 0.0156

Gnomad4 NFE AF: 0.0196

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0419 Hom.: 124

Bravo AF: 0.0742

Asia WGS AF: 0.129 AC: 448 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.2
DANN	Benign	0.91

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: rs10417943; hg19: chr19-55525337;