1-206775208-G-T

Position:

• chr1-206775208-G-T

Variant summary

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

The NM_153758.5(IL19):​c.-149+4130G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,454 control chromosomes in the GnomAD database, including 8,956 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 (8956 hom., cov: 30)
• Consequence: IL19 NM_153758.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.696

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL19	NM_153758.5	c.-149+4130G>T		intron_variant		ENST00000659997.3	NP_715639.2
IL19	NM_001393490.1	c.-149+4378G>T		intron_variant			NP_001380419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL19	ENST00000659997.3	c.-149+4130G>T		intron_variant			NM_153758.5	ENSP00000499459	P1
IL19	ENST00000656872.2	c.-149+4378G>T		intron_variant				ENSP00000499487	P1
IL19	ENST00000662320.1	n.67+4378G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50659 AN: 151336 Hom.: 8938 Cov.: 30

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.0517

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.335 AC: 50719 AN: 151454 Hom.: 8956 Cov.: 30 AF XY: 0.328 AC XY: 24310 AN XY: 74036

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.0517

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.310

Alfa AF: 0.137 Hom.: 239

Bravo AF: 0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.22

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6693899; hg19: chr1-206948553;