Genetic Variant BISPR:n.225+37_225+38insAGTCTGGGGGCGGGGCCTG (chr19-17406017-A-AGGGCCTGAGTCTGGGGGCG) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_001304547.2(MVB12A):c.-406-53_-406-52insAGTCTGGGGGCGGGGCCTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000946 in 151,232 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.00089 ( 2 hom., cov: 29)

Exomes 𝑓: 0.0033 ( 2 hom. )

Consequence

MVB12A
NM_001304547.2 intron

Scores

Not classified

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 0.137

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000892 (132/147936) while in subpopulation SAS AF = 0.0284 (129/4538). AF 95% confidence interval is 0.0244. There are 2 homozygotes in GnomAd4. There are 99 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position FAILED quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
MVB12A	NM_001304547.2 link	c.-406-53_-406-52insAGTCTGGGGGCGGGGCCTG	intron_variant	Intron 1 of 9	NP_001291476.1
BISPR	NR_130765.1 link	n.310+29_310+30insAGTCTGGGGGCGGGGCCTG	intron_variant	Intron 1 of 4
BISPR	NR_130766.1 link	n.87-53_87-52insAGTCTGGGGGCGGGGCCTG	intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
BISPR	ENST00000635435.2 link	n.225+37_225+38insAGTCTGGGGGCGGGGCCTG	intron_variant	Intron 1 of 3	1
MVB12A	ENST00000528604.5 link	c.-224-53_-224-52insAGTCTGGGGGCGGGGCCTG	intron_variant	Intron 1 of 6	3	ENSP00000435052.1	E9PLZ8
MVB12A	ENST00000528911.5 link	c.-406-53_-406-52insAGTCTGGGGGCGGGGCCTG	intron_variant	Intron 1 of 6	5	ENSP00000433280.1	E9PLL0

Frequencies

GnomAD3 genomes

AF:

0.000879

AC:

130

AN:

147820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000760

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0280

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00334

AC:

AN:

3296

Hom.:

Cov.:

AF XY:

0.00520

AC XY:

AN XY:

1924

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

268

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

Gnomad4 SAS exome

AF:

0.0182

AC:

AN:

606

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

Gnomad4 NFE exome

AF:

0.00

AC:

AN:

2044

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

168

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000892

AC:

132

AN:

147936

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

AN XY:

71944

show subpopulations

Gnomad4 AFR

AF:

0.0000758

AC:

0.0000757767

AN:

0.0000757767

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.0284

AC:

0.0284266

AN:

0.0284266

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00

AC:

AN:

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome 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

Alfa

AF:

0.000169

Hom.:

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HUMAN IMMUNODEFICIENCY VIRUS TYPE 1, RAPID PROGRESSION TO AIDS

Other:1

National AIDS Research Institute, National AIDS Research Institute

Significance:association

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=83/17

polymorphism

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over