ENST00000635435.2:n.225+44_226-28dupGGGGCGGGGCCTGGGTCTG

Variant names:

• chr19-17406017-A-AGGGCCTGGGTCTGGGGGCG
• rs3217318
• ENST00000635435.2:n.225+44_226-28dupGGGGCGGGGCCTGGGTCTG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 9 publications found

Genes affected

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

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]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635435.2. 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
	MVB12A	NM_001304547.2		c.-406-46_-406-28dupGGGGCGGGGCCTGGGTCTG		intron	N/A	NP_001291476.1
	BISPR	NR_130765.1		n.310+36_311-28dupGGGGCGGGGCCTGGGTCTG		intron	N/A
	BISPR	NR_130766.1		n.87-46_87-28dupGGGGCGGGGCCTGGGTCTG		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BISPR	ENST00000635435.2	TSL:1	n.225+44_226-28dupGGGGCGGGGCCTGGGTCTG		intron	N/A
	BISPR	ENST00000634731.2	TSL:3	n.256_274dupGGGGCGGGGCCTGGGTCTG		non_coding_transcript_exon	Exon 1 of 2
	BISPR	ENST00000635572.1	TSL:4	n.291_309dupGGGGCGGGGCCTGGGTCTG		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.177 AC: 25973 AN: 147042 Hom.: 2470 Cov.: 29

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: 55 AN: 3296 Hom.: 6 Cov.: 0 AF XY: 0.0187 AC XY: 36 AN XY: 1924

African (AFR) AF: 0.00 AC: 0 AN: 32

American (AMR) AF: 0.00746 AC: 2 AN: 268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 46

East Asian (EAS) AF: 0.00 AC: 0 AN: 42

South Asian (SAS) AF: 0.0611 AC: 37 AN: 606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 76

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.00587 AC: 12 AN: 2044

Other (OTH) AF: 0.0238 AC: 4 AN: 168

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.177 AC: 26015 AN: 147162 Hom.: 2472 Cov.: 29 AF XY: 0.179 AC XY: 12770 AN XY: 71528

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: 65 AN: 290

European-Non Finnish (NFE) AF: 0.130 AC: 8698 AN: 66972

Other (OTH) AF: 0.190 AC: 383 AN: 2018

Alfa AF: 0.0483 Hom.: 60

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs3217318; hg19: chr19-17516826;