chr10-22209280-A-G

Position:

• chr10-22209280-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394757.1(EBLN1):​c.704T>C​(p.Met235Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,589,788 control chromosomes in the GnomAD database, including 58,483 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/14 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 0.32 (8842 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49641 hom.)
• Consequence: EBLN1 NM_001394757.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200

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=9.234403E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBLN1	NM_001394757.1	c.704T>C	p.Met235Thr	missense_variant	3/3	ENST00000422359.3
EBLN1	NM_001199938.2	c.704T>C	p.Met235Thr	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBLN1	ENST00000422359.3	c.704T>C	p.Met235Thr	missense_variant	3/3		NM_001394757.1	P1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48913 AN: 152014 Hom.: 8815 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.310

GnomAD3 exomes AF: 0.258 AC: 54099 AN: 209552 Hom.: 7458 AF XY: 0.248 AC XY: 28748 AN XY: 115772

Gnomad AFR exome AF: 0.501

Gnomad AMR exome AF: 0.279

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.213

Gnomad SAS exome AF: 0.159

Gnomad FIN exome AF: 0.208

Gnomad NFE exome AF: 0.255

Gnomad OTH exome AF: 0.258

GnomAD4 exome AF: 0.258 AC: 370460 AN: 1437656 Hom.: 49641 Cov.: 33 AF XY: 0.254 AC XY: 181652 AN XY: 714528

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.270

GnomAD4 genome AF: 0.322 AC: 48989 AN: 152132 Hom.: 8842 Cov.: 32 AF XY: 0.318 AC XY: 23625 AN XY: 74382

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.310

Alfa AF: 0.265 Hom.: 12422

Bravo AF: 0.339

TwinsUK AF: 0.260 AC: 965

ALSPAC AF: 0.249 AC: 960

ExAC AF: 0.245 AC: 28961

Asia WGS AF: 0.268 AC: 932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.094
DANN	Benign	0.81
DEOGEN2	Benign	0.0011	T
FATHMM_MKL	Benign	0.000090	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.000092	T
MutationAssessor	Benign	-0.69	N
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	1.0	T
Vest4		0.039
MPC		0.63
GERP RS		0.51
Varity_R		0.13
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2243897; hg19: chr10-22498209; COSMIC: COSV69370307;