Genetic Variant ENSG00000267149:n.1001+6515C>A (chr19-55038390-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000585492.1(ENSG00000267149):n.1001+6515C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000196 in 509,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000020 ( 0 hom. )

Consequence

ENSG00000267149
ENST00000585492.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.58

Publications

0 publications found

Variant links:

Genes affected

ENSG00000267149 (HGNC:):

ENSG00000267149 links:

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

GP6-AS1 links:

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 Gene-Disease associations (from GenCC):

platelet-type bleeding disorder 11
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

GP6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000585492.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GP6	NM_016363.5	MANE Select	c.-154C>A	upstream_gene	N/A	NP_057447.5
GP6	NM_001083899.2		c.-154C>A	upstream_gene	N/A	NP_001077368.2
GP6	NM_001256017.2		c.-154C>A	upstream_gene	N/A	NP_001242946.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ENSG00000267149	ENST00000585492.1	TSL:2	n.1001+6515C>A	intron	N/A
GP6-AS1	ENST00000586845.1	TSL:3	n.134-4442G>T	intron	N/A
GP6-AS1	ENST00000586961.1	TSL:5	n.45-4442G>T	intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000196

AC:

AN:

509060

Hom.:

AF XY:

0.00

AC XY:

AN XY:

271868

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

14212

American (AMR)

AF:

0.00

AC:

AN:

27334

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16478

East Asian (EAS)

AF:

0.0000316

AC:

AN:

31608

South Asian (SAS)

AF:

0.00

AC:

AN:

55066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2252

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

300368

Other (OTH)

AF:

0.00

AC:

AN:

28426

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.024

(source)

DANN

Benign

0.71

PhyloP100

-2.6

PromoterAI

0.012

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over