rs428253

Positions:

• chr19-4229916-G-C

Variant summary

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

The NM_005755.3(EBI3):​c.67+299G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,876 control chromosomes in the GnomAD database, including 8,986 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8986 hom., cov: 31)
• Consequence: EBI3 NM_005755.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

Genes affected

EBI3 (HGNC:3129): (Epstein-Barr virus induced 3) This gene was identified by its induced expression in B lymphocytes in response Epstein-Barr virus infection. It encodes a secreted glycoprotein belonging to the hematopoietin receptor family, and heterodimerizes with a 28 kDa protein to form interleukin 27 (IL-27). IL-27 regulates T cell and inflammatory responses, in part by activating the Jak/STAT pathway of CD4+ T cells. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBI3	NM_005755.3	c.67+299G>C		intron_variant		ENST00000221847.6	NP_005746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBI3	ENST00000221847.6	c.67+299G>C		intron_variant		1	NM_005755.3	ENSP00000221847	P1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49672 AN: 151758 Hom.: 8971 Cov.: 31

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.311

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.327 AC: 49721 AN: 151876 Hom.: 8986 Cov.: 31 AF XY: 0.321 AC XY: 23839 AN XY: 74260

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.309

Alfa AF: 0.308 Hom.: 989

Bravo AF: 0.333

Asia WGS AF: 0.250 AC: 871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.95
DANN	Benign	0.14

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: rs428253; hg19: chr19-4229913;