10-22209110-C-T

Variant names:

• chr10-22209110-C-T
• rs535527471
• NM_001394757.1:c.874G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394757.1(EBLN1):​c.874G>A​(p.Val292Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,384,086 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. V292L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EBLN1 NM_001394757.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07586452).

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.874G>A	p.Val292Met	missense	Exon 3 of 3	NP_001381686.1	P0CF75
	EBLN1	NM_001199938.2		c.874G>A	p.Val292Met	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.874G>A	p.Val292Met	missense	Exon 3 of 3	ENSP00000473842.1	P0CF75
	EBLN1	ENST00000939589.1		c.874G>A	p.Val292Met	missense	Exon 2 of 2	ENSP00000609648.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1384086 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 682954

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078886

Other (OTH) AF: 0.0000173 AC: 1 AN: 57908

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.1
DANN	Benign	0.62
DEOGEN2	Benign	0.0016	T
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.076	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.26
PrimateAI	Benign	0.45	T
Sift4G	Benign	0.082	T
Vest4		0.074
MVP		0.19
MPC		0.55
GERP RS		-0.60
Varity_R		0.14
gMVP		0.19
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs535527471; hg19: chr10-22498039;