rs229515

Variant names:

• chr22-37180032-C-T
• rs229515
• ENST00000419128.2:n.223-2397C>T

Variant summary

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

The NR_199008.1(IL2RB-AS1):​n.207-2397C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,240 control chromosomes in the GnomAD database, including 11,173 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 0.36 (11171 hom., cov: 34)
  • Exomes 𝑓: 0.35 (2 hom.)
• Consequence: IL2RB-AS1 NR_199008.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509
• Publications: 5 publications found

Genes affected

IL2RB-AS1 (HGNC:40300):

C1QTNF6 (HGNC:14343): (C1q and TNF related 6) Predicted to enable identical protein binding activity. Predicted to be located in extracellular space. Predicted to be integral component of membrane. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_199008.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RB-AS1	NR_199008.1		n.207-2397C>T		intron	N/A
	C1QTNF6	NM_031910.4	MANE Select	c.*2156G>A		downstream_gene	N/A	NP_114116.3
	C1QTNF6	NM_182486.2		c.*872G>A		downstream_gene	N/A	NP_872292.1	Q9BXI9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL2RB-AS1	ENST00000419128.2	TSL:5	n.223-2397C>T		intron	N/A
	C1QTNF6	ENST00000337843.7	TSL:1 MANE Select	c.*2156G>A		downstream_gene	N/A	ENSP00000338812.2	Q9BXI9-2
	C1QTNF6	ENST00000397110.6	TSL:1	c.*872G>A		downstream_gene	N/A	ENSP00000380299.2	Q9BXI9-2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55318 AN: 152074 Hom.: 11134 Cov.: 34

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.354 AC: 17 AN: 48 Hom.: 2 AF XY: 0.361 AC XY: 13 AN XY: 36

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.292 AC: 7 AN: 24

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.300 AC: 3 AN: 10

Other (OTH) AF: 0.500 AC: 6 AN: 12

GnomAD4 genome AF: 0.364 AC: 55428 AN: 152192 Hom.: 11171 Cov.: 34 AF XY: 0.367 AC XY: 27285 AN XY: 74396

African (AFR) AF: 0.516 AC: 21424 AN: 41490

American (AMR) AF: 0.428 AC: 6557 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3472

East Asian (EAS) AF: 0.492 AC: 2545 AN: 5174

South Asian (SAS) AF: 0.367 AC: 1772 AN: 4824

European-Finnish (FIN) AF: 0.260 AC: 2755 AN: 10602

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17917 AN: 68008

Other (OTH) AF: 0.384 AC: 810 AN: 2112

Alfa AF: 0.328 Hom.: 3385

Bravo AF: 0.387

Asia WGS AF: 0.457 AC: 1588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.69
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs229515; hg19: chr22-37576072;