chr19-4237428-A-T

Variant names:

• chr19-4237428-A-T
• rs6613
• NM_005755.3:c.*340A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005755.3(EBI3):​c.*340A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 166,364 control chromosomes in the GnomAD database, including 8,914 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 (8376 hom., cov: 32)
  • Exomes 𝑓: 0.27 (538 hom.)
• Consequence: EBI3 NM_005755.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBI3	NM_005755.3	c.*340A>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000221847.6	NP_005746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBI3	ENST00000221847.6	c.*340A>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_005755.3	ENSP00000221847.4

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49537 AN: 151812 Hom.: 8359 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.274 AC: 3952 AN: 14434 Hom.: 538 Cov.: 0 AF XY: 0.275 AC XY: 1994 AN XY: 7256

African (AFR) AF: 0.341 AC: 174 AN: 510

American (AMR) AF: 0.226 AC: 86 AN: 380

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 215 AN: 670

East Asian (EAS) AF: 0.354 AC: 356 AN: 1006

South Asian (SAS) AF: 0.388 AC: 52 AN: 134

European-Finnish (FIN) AF: 0.259 AC: 143 AN: 552

Middle Eastern (MID) AF: 0.325 AC: 26 AN: 80

European-Non Finnish (NFE) AF: 0.258 AC: 2610 AN: 10116

Other (OTH) AF: 0.294 AC: 290 AN: 986

GnomAD4 genome AF: 0.326 AC: 49577 AN: 151930 Hom.: 8376 Cov.: 32 AF XY: 0.326 AC XY: 24239 AN XY: 74268

African (AFR) AF: 0.377 AC: 15616 AN: 41422

American (AMR) AF: 0.291 AC: 4433 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3470

East Asian (EAS) AF: 0.452 AC: 2336 AN: 5164

South Asian (SAS) AF: 0.460 AC: 2214 AN: 4808

European-Finnish (FIN) AF: 0.285 AC: 3016 AN: 10586

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19650 AN: 67932

Other (OTH) AF: 0.338 AC: 713 AN: 2112

Alfa AF: 0.302 Hom.: 873

Bravo AF: 0.326

Asia WGS AF: 0.452 AC: 1570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.68
PhyloP100		-0.066
Mutation Taster		=100/0	polymorphism (auto)

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: rs6613; hg19: chr19-4237425;