NM_004855.5:c.-16A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004855.5(PIGB):c.-16A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,597,260 control chromosomes in the GnomAD database, including 37,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4515 hom., cov: 32)

Exomes 𝑓: 0.20 ( 32746 hom. )

Consequence

PIGB
NM_004855.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.339

Publications

12 publications found

Variant links:

Genes affected

PIGB (HGNC:8959): (phosphatidylinositol glycan anchor biosynthesis class B) This gene encodes a transmembrane protein that is located in the endoplasmic reticulum and is involved in GPI-anchor biosynthesis. The glycosylphosphatidylinositol (GPI) anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This gene is thought to encode a member of a family of dolichol-phosphate-mannose (Dol-P-Man) dependent mannosyltransferases. [provided by RefSeq, Jul 2008]

PIGB links:

PIGBOS1 (HGNC:50696): (PIGB opposite strand 1) Involved in regulation of endoplasmic reticulum unfolded protein response. Is integral component of mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

PIGBOS1 links:

RAB27A (HGNC:9766): (RAB27A, member RAS oncogene family) The protein encoded by this gene belongs to the small GTPase superfamily, Rab family. The protein is membrane-bound and may be involved in protein transport and small GTPase mediated signal transduction. Mutations in this gene are associated with Griscelli syndrome type 2. Alternative splicing occurs at this locus and four transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

RAB27A Gene-Disease associations (from GenCC):

Griscelli syndrome type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

RAB27A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 15-55319235-A-G is Benign according to our data. Variant chr15-55319235-A-G is described in ClinVar as Benign. ClinVar VariationId is 1327019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004855.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PIGB	NM_004855.5	MANE Select	c.-16A>G	5_prime_UTR	Exon 1 of 12	NP_004846.4
PIGBOS1	NM_001308421.2	MANE Select	c.-447T>C	upstream_gene	N/A	NP_001295350.1
RAB27A	NM_001438970.1		c.-536T>C	upstream_gene	N/A	NP_001425899.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PIGB	ENST00000164305.10	TSL:1 MANE Select	c.-16A>G	5_prime_UTR	Exon 1 of 12	ENSP00000164305.5
PIGB	ENST00000858252.1		c.-16A>G	5_prime_UTR	Exon 1 of 12	ENSP00000528311.1
PIGB	ENST00000919400.1		c.-16A>G	5_prime_UTR	Exon 1 of 12	ENSP00000589459.1

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34931

AN:

152058

Hom.:

4507

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.549

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.235

GnomAD2 exomes

AF:

0.242

AC:

53676

AN:

221532

AF XY:

0.237

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.322

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.575

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.223

GnomAD4 exome

AF:

0.201

AC:

289767

AN:

1445084

Hom.:

32746

Cov.:

AF XY:

0.201

AC XY:

144396

AN XY:

717112

show subpopulations

African (AFR)

AF:

0.268

AC:

8919

AN:

33276

American (AMR)

AF:

0.313

AC:

13197

AN:

42116

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

4600

AN:

25494

East Asian (EAS)

AF:

0.527

AC:

20626

AN:

39172

South Asian (SAS)

AF:

0.274

AC:

22789

AN:

83078

European-Finnish (FIN)

AF:

0.174

AC:

9107

AN:

52266

Middle Eastern (MID)

AF:

0.163

AC:

931

AN:

5726

European-Non Finnish (NFE)

AF:

0.178

AC:

196722

AN:

1104228

Other (OTH)

AF:

0.216

AC:

12876

AN:

59728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

10104

20207

30311

40414

50518

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7316

14632

21948

29264

36580

<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

AF:

0.230

AC:

34960

AN:

152176

Hom.:

4515

Cov.:

AF XY:

0.233

AC XY:

17297

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.270

AC:

11194

AN:

41488

American (AMR)

AF:

0.266

AC:

4064

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

671

AN:

3470

East Asian (EAS)

AF:

0.548

AC:

2837

AN:

5174

South Asian (SAS)

AF:

0.290

AC:

1403

AN:

4830

European-Finnish (FIN)

AF:

0.176

AC:

1862

AN:

10582

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.178

AC:

12138

AN:

68012

Other (OTH)

AF:

0.233

AC:

493

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1351

2703

4054

5406

6757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.195

Hom.:

1116

Bravo

AF:

0.241

Asia WGS

AF:

0.378

AC:

1315

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Developmental and epileptic encephalopathy, 80 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.4

(source)

DANN

Benign

0.63

PhyloP100

0.34

PromoterAI

-0.060

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over