10-22209539-C-T

Variant names:

• chr10-22209539-C-T
• rs838759
• NM_001394757.1:c.445G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394757.1(EBLN1):​c.445G>A​(p.Gly149Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,559,946 control chromosomes in the GnomAD database, including 44,016 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (4630 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39386 hom.)
• Consequence: EBLN1 NM_001394757.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 13 publications found

Genes affected

EBLN1 (HGNC:39430): (endogenous Bornavirus like nucleoprotein 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005245656).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394757.1. 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
	EBLN1	NM_001394757.1	MANE Select	c.445G>A	p.Gly149Arg	missense	Exon 3 of 3	NP_001381686.1
	EBLN1	NM_001199938.2		c.445G>A	p.Gly149Arg	missense	Exon 1 of 1	NP_001186867.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBLN1	ENST00000422359.3	TSL:6 MANE Select	c.445G>A	p.Gly149Arg	missense	Exon 3 of 3	ENSP00000473842.1
	EBLN1	ENST00000939589.1		c.445G>A	p.Gly149Arg	missense	Exon 2 of 2	ENSP00000609648.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 36934 AN: 149864 Hom.: 4621 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.247

GnomAD2 exomes AF: 0.229 AC: 37651 AN: 164578 AF XY: 0.222

Gnomad AFR exome AF: 0.289

Gnomad AMR exome AF: 0.257

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.212

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.244

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.234 AC: 329798 AN: 1409986 Hom.: 39386 Cov.: 33 AF XY: 0.231 AC XY: 161525 AN XY: 698394

African (AFR) AF: 0.267 AC: 8736 AN: 32728

American (AMR) AF: 0.261 AC: 9924 AN: 38070

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 5985 AN: 25498

East Asian (EAS) AF: 0.179 AC: 6792 AN: 38050

South Asian (SAS) AF: 0.154 AC: 12673 AN: 82050

European-Finnish (FIN) AF: 0.198 AC: 7044 AN: 35584

Middle Eastern (MID) AF: 0.171 AC: 980 AN: 5728

European-Non Finnish (NFE) AF: 0.241 AC: 263940 AN: 1093216

Other (OTH) AF: 0.232 AC: 13724 AN: 59062

GnomAD4 genome AF: 0.246 AC: 36958 AN: 149960 Hom.: 4630 Cov.: 32 AF XY: 0.245 AC XY: 17975 AN XY: 73370

African (AFR) AF: 0.284 AC: 11208 AN: 39488

American (AMR) AF: 0.270 AC: 4110 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 780 AN: 3442

East Asian (EAS) AF: 0.201 AC: 1038 AN: 5176

South Asian (SAS) AF: 0.163 AC: 785 AN: 4810

European-Finnish (FIN) AF: 0.190 AC: 2002 AN: 10558

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16054 AN: 67940

Other (OTH) AF: 0.248 AC: 521 AN: 2100

Alfa AF: 0.237 Hom.: 14907

Bravo AF: 0.253

TwinsUK AF: 0.245 AC: 910

ALSPAC AF: 0.232 AC: 895

ExAC AF: 0.190 AC: 21643

Asia WGS AF: 0.238 AC: 828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	7.6
DANN	Benign	0.63
DEOGEN2	Benign	0.083	T
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0052	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.010
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.19	T
Vest4		0.089
MPC		0.65
GERP RS		0.51
Varity_R		0.095
gMVP		0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs838759; hg19: chr10-22498468; COSMIC: COSV69370310;