chr19-55032557-G-A

Variant names:

• chr19-55032557-G-A
• rs189534942
• NM_016363.5:c.35-19C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_016363.5(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_016363.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.20
• Publications: 1 publications found

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]

ENSG00000267149 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016363.5. 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
	GP6	NM_016363.5	MANE Select	c.35-19C>T		intron	N/A	NP_057447.5
	GP6	NM_001083899.2		c.35-19C>T		intron	N/A	NP_001077368.2
	GP6	NM_001256017.2		c.35-19C>T		intron	N/A	NP_001242946.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	ENST00000417454.5	TSL:1 MANE Select	c.35-19C>T		intron	N/A	ENSP00000394922.1
	GP6	ENST00000310373.7	TSL:1	c.35-19C>T		intron	N/A	ENSP00000308782.3
	GP6	ENST00000333884.2	TSL:1	c.35-19C>T		intron	N/A	ENSP00000334552.2

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

GnomAD2 exomes AF: 0.00914 AC: 2220 AN: 243012 AF XY: 0.00927

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 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

African (AFR) AF: 0.00158 AC: 53 AN: 33468

American (AMR) AF: 0.00361 AC: 161 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00677 AC: 177 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39692

South Asian (SAS) AF: 0.00700 AC: 603 AN: 86156

European-Finnish (FIN) AF: 0.0220 AC: 1165 AN: 53024

Middle Eastern (MID) AF: 0.00712 AC: 41 AN: 5760

European-Non Finnish (NFE) AF: 0.0119 AC: 13271 AN: 1111730

Other (OTH) AF: 0.00948 AC: 572 AN: 60364

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

African (AFR) AF: 0.00190 AC: 79 AN: 41594

American (AMR) AF: 0.00353 AC: 54 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00600 AC: 29 AN: 4830

European-Finnish (FIN) AF: 0.0218 AC: 232 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0124 AC: 845 AN: 68022

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.0104 Hom.: 3

Bravo AF: 0.00679

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.66
PhyloP100		-1.2
PromoterAI		0.056	Neutral
Mutation Taster		=100/0	polymorphism

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: rs189534942; hg19: chr19-55543925;