10-22209571-C-T

Variant names:

• chr10-22209571-C-T
• rs765282974
• NM_001394757.1:c.413G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394757.1(EBLN1):​c.413G>A​(p.Arg138His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000596 in 1,542,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R138P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000060 (0 hom.)
• Consequence: EBLN1 NM_001394757.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04274425).

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.413G>A	p.Arg138His	missense	Exon 3 of 3	NP_001381686.1	P0CF75
	EBLN1	NM_001199938.2		c.413G>A	p.Arg138His	missense	Exon 1 of 1	NP_001186867.1	P0CF75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBLN1	ENST00000422359.3	TSL:6 MANE Select	c.413G>A	p.Arg138His	missense	Exon 3 of 3	ENSP00000473842.1	P0CF75
	EBLN1	ENST00000939589.1		c.413G>A	p.Arg138His	missense	Exon 2 of 2	ENSP00000609648.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000654 AC: 9 AN: 137652 AF XY: 0.0000532

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000404

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000181

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000374

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000597 AC: 83 AN: 1390392 Hom.: 0 Cov.: 33 AF XY: 0.0000422 AC XY: 29 AN XY: 686748

African (AFR) AF: 0.00 AC: 0 AN: 31908

American (AMR) AF: 0.0000277 AC: 1 AN: 36066

Ashkenazi Jewish (ASJ) AF: 0.0000792 AC: 2 AN: 25250

East Asian (EAS) AF: 0.0000548 AC: 2 AN: 36488

South Asian (SAS) AF: 0.0000625 AC: 5 AN: 79960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.0000674 AC: 73 AN: 1082610

Other (OTH) AF: 0.00 AC: 0 AN: 58238

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74414

African (AFR) AF: 0.0000241 AC: 1 AN: 41514

American (AMR) AF: 0.0000653 AC: 1 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000106

ExAC AF: 0.0000365 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.19
DANN	Benign	0.87
DEOGEN2	Benign	0.0069	T
FATHMM_MKL	Benign	0.00084	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.043	T
MutationAssessor	Benign	0.69	N
PhyloP100		-2.3
PrimateAI	Benign	0.37	T
Sift4G	Benign	0.083	T
Vest4		0.029
MVP		0.12
MPC		0.74
GERP RS		-1.0
Varity_R		0.054
gMVP		0.23
Mutation Taster		=100/0	polymorphism

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: rs765282974; hg19: chr10-22498500; COSMIC: COSV69370237;