4-122676016-T-C

Position:

• chr4-122676016-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000417927.1(IL21-AS1):​n.3129-12521T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 152,258 control chromosomes in the GnomAD database, including 64 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 0.023 (64 hom., cov: 32)
• Consequence: IL21-AS1 ENST00000417927.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890

Genes affected

IL21-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0232 (3531/152258) while in subpopulation NFE AF= 0.039 (2650/68020). AF 95% confidence interval is 0.0377. There are 64 homozygotes in gnomad4. There are 1623 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 64 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL21-AS1	NR_104126.1	n.3129-12521T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL21-AS1	ENST00000417927.1	n.3129-12521T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0232 AC: 3532 AN: 152140 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.00550

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00954

Gnomad FIN AF: 0.0293

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0158

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

GnomAD4 genome AF: 0.0232 AC: 3531 AN: 152258 Hom.: 64 Cov.: 32 AF XY: 0.0218 AC XY: 1623 AN XY: 74442

Gnomad4 AFR AF: 0.00549

Gnomad4 AMR AF: 0.0123

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00934

Gnomad4 FIN AF: 0.0293

Gnomad4 NFE AF: 0.0390

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0354 Hom.: 24

Bravo AF: 0.0200

Asia WGS AF: 0.00578 AC: 20 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13147359; hg19: chr4-123597171;