rs4072226

Positions:

• chr1-206784104-T-C
• chr1-206784104-T-G

Variant summary

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

The NM_153758.5(IL19):​c.-149+13026T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,028 control chromosomes in the GnomAD database, including 29,414 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 0.61 (29414 hom., cov: 31)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL19	NM_153758.5	c.-149+13026T>C		intron_variant		ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-149+13274T>C		intron_variant			NP_001380419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.-149+13026T>C		intron_variant			NM_153758.5	ENSP00000499459	P1
IL19	ENST00000656872.2	c.-149+13274T>C		intron_variant				ENSP00000499487	P1
IL19	ENST00000662320.1	n.67+13274T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93231 AN: 151910 Hom.: 29398 Cov.: 31

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.614 AC: 93270 AN: 152028 Hom.: 29414 Cov.: 31 AF XY: 0.621 AC XY: 46148 AN XY: 74308

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.653

Alfa AF: 0.595 Hom.: 13257

Bravo AF: 0.622

Asia WGS AF: 0.808 AC: 2812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.76
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4072226; hg19: chr1-206957449; COSMIC: COSV60019535;