10-22209539-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 10/14 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

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBLN1	NM_001394757.1	c.445G>A	p.Gly149Arg	missense_variant	Exon 3 of 3	ENST00000422359.3	NP_001381686.1
EBLN1	NM_001199938.2	c.445G>A	p.Gly149Arg	missense_variant	Exon 1 of 1		NP_001186867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBLN1	ENST00000422359.3	c.445G>A	p.Gly149Arg	missense_variant	Exon 3 of 3	6	NM_001394757.1	ENSP00000473842.1

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

GnomAD3 exomes AF: 0.229 AC: 37651 AN: 164578 Hom.: 4299 AF XY: 0.222 AC XY: 20098 AN XY: 90338

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 SAS exome AF: 0.152

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

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.232

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

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.248

Alfa AF: 0.234 Hom.: 9956

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 v4.3

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
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

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

Publications

LitVar

Other links and lift over

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