Genetic Variant BISPR:n.225+44_226-28dupGGGGCGGGGCCTGGGTCTG (chr19-17406017-A-AGGGCCTGGGTCTGGGGGCG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The ENST00000635435.2(BISPR):n.225+44_226-28dupGGGGCGGGGCCTGGGTCTG variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2472 hom., cov: 29)

Exomes 𝑓: 0.017 ( 6 hom. )

Failed GnomAD Quality Control

Consequence

BISPR
ENST00000635435.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.137

Publications

9 publications found

Variant links:

Genes affected

BISPR (HGNC:51290): (BST2 interferon stimulated positive regulator)

BISPR links:

MVB12A (HGNC:25153): (multivesicular body subunit 12A) Enables lipid binding activity and ubiquitin binding activity. Involved in regulation of epidermal growth factor receptor signaling pathway; viral budding; and virus maturation. Located in several cellular components, including Golgi apparatus; centrosome; and nucleoplasm. Part of ESCRT I complex. [provided by Alliance of Genome Resources, Apr 2022]

MVB12A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0167 (55/3296) while in subpopulation SAS AF = 0.0611 (37/606). AF 95% confidence interval is 0.0455. There are 6 homozygotes in GnomAdExome4. There are 36 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
MVB12A	NM_001304547.2 link	c.-406-46_-406-28dupGGGGCGGGGCCTGGGTCTG	intron_variant	Intron 1 of 9	NP_001291476.1
BISPR	NR_130765.1 link	n.310+36_311-28dupGGGGCGGGGCCTGGGTCTG	intron_variant	Intron 1 of 4
BISPR	NR_130766.1 link	n.87-46_87-28dupGGGGCGGGGCCTGGGTCTG	intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
BISPR	ENST00000635435.2 link	n.225+44_226-28dupGGGGCGGGGCCTGGGTCTG	intron_variant	Intron 1 of 3	1
BISPR	ENST00000634731.2 link	n.256_274dupGGGGCGGGGCCTGGGTCTG	non_coding_transcript_exon_variant	Exon 1 of 2	3
BISPR	ENST00000635572.1 link	n.291_309dupGGGGCGGGGCCTGGGTCTG	non_coding_transcript_exon_variant	Exon 1 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

25973

AN:

147042

Hom.:

2470

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.0633

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.213

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.224

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.186

GnomAD4 exome

AF:

0.0167

AC:

AN:

3296

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

AN XY:

1924

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00746

AC:

AN:

268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0611

AC:

AN:

606

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00587

AC:

AN:

2044

Other (OTH)

AF:

0.0238

AC:

AN:

168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.177

AC:

26015

AN:

147162

Hom.:

2472

Cov.:

AF XY:

0.179

AC XY:

12770

AN XY:

71528

show subpopulations

African (AFR)

AF:

0.253

AC:

9942

AN:

39332

American (AMR)

AF:

0.187

AC:

2763

AN:

14742

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

702

AN:

3402

East Asian (EAS)

AF:

0.176

AC:

878

AN:

4982

South Asian (SAS)

AF:

0.214

AC:

964

AN:

4506

European-Finnish (FIN)

AF:

0.156

AC:

1563

AN:

10018

Middle Eastern (MID)

AF:

0.224

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.130

AC:

8698

AN:

66972

Other (OTH)

AF:

0.190

AC:

383

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

890

1780

2670

3560

4450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.0483

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.14

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

19-17406017-AGGGCCTGGGTCTGGGGGCG-AGGGCCTGGGTCTGGGGGCGGGGCCTGGGTCTGGGGGCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over