rs6676671

Positions:

• chr1-206779403-T-A

Variant summary

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

The NM_153758.5(IL19):​c.-149+8325T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,948 control chromosomes in the GnomAD database, including 8,118 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 0.31 (8118 hom., cov: 30)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL19	NM_153758.5	c.-149+8325T>A		intron_variant		ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-149+8573T>A		intron_variant			NP_001380419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.-149+8325T>A		intron_variant			NM_153758.5	ENSP00000499459	P1
IL19	ENST00000656872.2	c.-149+8573T>A		intron_variant				ENSP00000499487	P1
IL19	ENST00000662320.1	n.67+8573T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47403 AN: 151830 Hom.: 8116 Cov.: 30

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.0314

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.312 AC: 47417 AN: 151948 Hom.: 8118 Cov.: 30 AF XY: 0.305 AC XY: 22635 AN XY: 74270

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.0311

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.287

Alfa AF: 0.349 Hom.: 1185

Bravo AF: 0.299

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6676671; hg19: chr1-206952748;