rs6703630

Variant names:

• chr1-206775294-C-T
• rs6703630
• NM_153758.5:c.-149+4216C>T

Variant summary

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

The NM_153758.5(IL19):​c.-149+4216C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 151,876 control chromosomes in the GnomAD database, including 4,720 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 0.24 (4720 hom., cov: 31)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.71
• Publications: 30 publications found

Genes affected

IL19 (HGNC:5990): (interleukin 19) The protein encoded by this gene is a cytokine that belongs to the IL10 cytokine subfamily. This cytokine is found to be preferentially expressed in monocytes. It can bind the IL20 receptor complex and lead to the activation of the signal transducer and activator of transcription 3 (STAT3). A similar cytokine in mouse is reported to up-regulate the expression of IL6 and TNF-alpha and induce apoptosis, which suggests a role of this cytokine in inflammatory responses. Alternatively spliced transcript variants encoding the distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL19	NM_153758.5	c.-149+4216C>T		intron_variant	Intron 1 of 6	ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-149+4464C>T		intron_variant	Intron 1 of 6		NP_001380419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.-149+4216C>T		intron_variant	Intron 1 of 6		NM_153758.5	ENSP00000499459.2
IL19	ENST00000656872.2	c.-149+4464C>T		intron_variant	Intron 1 of 6			ENSP00000499487.2
IL19	ENST00000662320.1	n.67+4464C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36387 AN: 151758 Hom.: 4713 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.00463

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.240 AC: 36432 AN: 151876 Hom.: 4720 Cov.: 31 AF XY: 0.233 AC XY: 17285 AN XY: 74186

African (AFR) AF: 0.264 AC: 10935 AN: 41368

American (AMR) AF: 0.170 AC: 2601 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 602 AN: 3470

East Asian (EAS) AF: 0.00464 AC: 24 AN: 5168

South Asian (SAS) AF: 0.113 AC: 543 AN: 4810

European-Finnish (FIN) AF: 0.243 AC: 2557 AN: 10538

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18440 AN: 67934

Other (OTH) AF: 0.197 AC: 415 AN: 2110

Alfa AF: 0.258 Hom.: 664

Bravo AF: 0.236

Asia WGS AF: 0.103 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.25
DANN	Benign	0.30
PhyloP100		-3.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6703630; hg19: chr1-206948639;