rs8126756

Positions:

• chr21-33403138-T-C
• chr21-33403138-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001329128.2(IFNGR2):​c.-406T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 147,368 control chromosomes in the GnomAD database, including 5,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5868 hom., cov: 27)
  • Exomes 𝑓: 0.099 (3 hom.)
• Consequence: IFNGR2 NM_001329128.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.194

Genes affected

IFNGR2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 21-33403138-T-C is Benign according to our data. Variant chr21-33403138-T-C is described in ClinVar as [Benign]. Clinvar id is 1289403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNGR2	NM_001329128.2	c.-406T>C		5_prime_UTR_variant	1/8		NP_001316057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.244 AC: 35825 AN: 147100 Hom.: 5854 Cov.: 27

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.109

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.0989 AC: 18 AN: 182 Hom.: 3 Cov.: 0 AF XY: 0.0820 AC XY: 10 AN XY: 122

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0921

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.244 AC: 35865 AN: 147186 Hom.: 5868 Cov.: 27 AF XY: 0.245 AC XY: 17535 AN XY: 71690

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.200

Alfa AF: 0.176 Hom.: 437

Bravo AF: 0.252

Asia WGS AF: 0.358 AC: 1193 AN: 3340

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.3
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8126756; hg19: chr21-34775444; COSMIC: COSV51641381; COSMIC: COSV51641381;