rs4657616

Positions:

• chr1-159001296-A-G

Variant summary

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

The NM_001320010.2(PYDC5):​c.-984T>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 0.317 in 152,122 control chromosomes in the GnomAD database, including 9,596 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 0.32 (9596 hom., cov: 32)
• Consequence: PYDC5 NM_001320010.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

Genes affected

PYDC5 (HGNC:53781): (pyrin domain containing 5) Predicted to enable double-stranded DNA binding activity. Involved in cellular response to interferon-beta; cellular response to virus; and negative regulation of protein-containing complex assembly. Predicted to be part of AIM2 inflammasome complex. [provided by Alliance of Genome Resources, Apr 2022]

IFI16 (HGNC:5395): (interferon gamma inducible protein 16) This gene encodes a member of the HIN-200 (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats) family of cytokines. The encoded protein contains domains involved in DNA binding, transcriptional regulation, and protein-protein interactions. The protein localizes to the nucleoplasm and nucleoli, and interacts with p53 and retinoblastoma-1. It modulates p53 function, and inhibits cell growth in the Ras/Raf signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYDC5	NM_001320010.2	c.-984T>C		5_prime_UTR_variant	1/1	ENST00000696987.1	NP_001306939.1
IFI16	NM_001364867.2	c.-180+901A>G		intron_variant			NP_001351796.1
IFI16	NM_001376588.1	c.-180+901A>G		intron_variant			NP_001363517.1
IFI16	NM_001376591.1	c.-180+901A>G		intron_variant			NP_001363520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYDC5	ENST00000696987.1	c.-984T>C		5_prime_UTR_variant	1/1		NM_001320010.2	ENSP00000513023.1
IFI16	ENST00000566111.5	c.-180+901A>G		intron_variant		2		ENSP00000458084.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48151 AN: 152004 Hom.: 9593 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.317 AC: 48166 AN: 152122 Hom.: 9596 Cov.: 32 AF XY: 0.317 AC XY: 23580 AN XY: 74368

Gnomad4 AFR AF: 0.0761

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.350

Alfa AF: 0.390 Hom.: 16228

Bravo AF: 0.325

Asia WGS AF: 0.352 AC: 1219 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.35
DANN	Benign	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4657616; hg19: chr1-158971086;