rs3832186

Variant names:

• chr3-73062330-C-CA
• rs3832186
• NM_018029.4:c.250dupA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_018029.4(EBLN2):​c.250dupA​(p.Arg84LysfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,607,514 control chromosomes in the GnomAD database, including 17,201 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1549 hom., cov: 30)
  • Exomes 𝑓: 0.13 (15652 hom.)
• Consequence: EBLN2 NM_018029.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 4 publications found

Genes affected

EBLN2 (HGNC:25493): (endogenous Bornavirus like nucleoprotein 2)

PPP4R2 (HGNC:18296): (protein phosphatase 4 regulatory subunit 2) The protein encoded by this gene is a regulatory subunit of the serine/threonine-protein phosphatase 4 complex. In addition to being required for efficient DNA double strand break repair, this complex plays a role in organization of microtubules at centrosomes and processing of spliceosomal snRNPs. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

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

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018029.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBLN2	NM_018029.4	MANE Select	c.250dupA	p.Arg84LysfsTer18	frameshift	Exon 1 of 1	NP_060499.3	Q6P2I7
	PPP4R2	NM_174907.4	MANE Select	c.419+1271dupA		intron	N/A	NP_777567.1	Q9NY27-1
	PPP4R2	NM_001318026.2		c.305+1271dupA		intron	N/A	NP_001304955.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBLN2	ENST00000533473.1	TSL:6 MANE Select	c.250dupA	p.Arg84LysfsTer18	frameshift	Exon 1 of 1	ENSP00000432104.1	Q6P2I7
	PPP4R2	ENST00000356692.10	TSL:1 MANE Select	c.419+1271dupA		intron	N/A	ENSP00000349124.5	Q9NY27-1
	PPP4R2	ENST00000710398.1		c.524+1271dupA		intron	N/A	ENSP00000518252.1	A0AA34QVI2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19605 AN: 152038 Hom.: 1549 Cov.: 30

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.0894

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.128

GnomAD2 exomes AF: 0.148 AC: 34705 AN: 235026 AF XY: 0.155

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0953

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.345

Gnomad FIN exome AF: 0.0832

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.129 AC: 187598 AN: 1455358 Hom.: 15652 Cov.: 62 AF XY: 0.135 AC XY: 98066 AN XY: 723838

African (AFR) AF: 0.107 AC: 3538 AN: 33054

American (AMR) AF: 0.100 AC: 4272 AN: 42706

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 4557 AN: 25918

East Asian (EAS) AF: 0.344 AC: 13609 AN: 39602

South Asian (SAS) AF: 0.325 AC: 27640 AN: 85024

European-Finnish (FIN) AF: 0.0902 AC: 4801 AN: 53242

Middle Eastern (MID) AF: 0.265 AC: 1520 AN: 5730

European-Non Finnish (NFE) AF: 0.107 AC: 118489 AN: 1110006

Other (OTH) AF: 0.153 AC: 9172 AN: 60076

GnomAD4 genome AF: 0.129 AC: 19630 AN: 152156 Hom.: 1549 Cov.: 30 AF XY: 0.132 AC XY: 9829 AN XY: 74362

African (AFR) AF: 0.108 AC: 4504 AN: 41526

American (AMR) AF: 0.119 AC: 1820 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3472

East Asian (EAS) AF: 0.363 AC: 1873 AN: 5162

South Asian (SAS) AF: 0.336 AC: 1617 AN: 4816

European-Finnish (FIN) AF: 0.0894 AC: 945 AN: 10570

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7824 AN: 68002

Other (OTH) AF: 0.131 AC: 276 AN: 2114

Alfa AF: 0.131 Hom.: 1044

Bravo AF: 0.125

Asia WGS AF: 0.341 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35
Mutation Taster		=26/74	disease causing

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

Other links and lift over

dbSNP: rs3832186; hg19: chr3-73111481; COSMIC: COSV55593932; COSMIC: COSV55593932;