rs1102000

Positions:

• chr1-158963117-G-A
• chr1-158963117-G-C

Variant summary

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

The NM_152501.5(PYHIN1):​c.1360-10530G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 152,138 control chromosomes in the GnomAD database, including 65,664 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 0.92 (65664 hom., cov: 30)
• Consequence: PYHIN1 NM_152501.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336

Genes affected

PYHIN1 (HGNC:28894): (pyrin and HIN domain family member 1) The protein encoded by this gene belongs to the HIN-200 family of interferon-inducible proteins that share a 200-amino acid signature motif at their C-termini. HIN200 proteins are primarily nuclear and are involved in transcriptional regulation of genes important for cell cycle control, differentiation, and apoptosis. Downregulation of this gene is associated with breast cancer. This protein acts as a tumor suppressor by promoting ubiquitination and subsequent degradation of MDM2, which leads to stabilization of p53/TP53. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYHIN1	NM_152501.5	c.1360-10530G>A		intron_variant		ENST00000368140.6	NP_689714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYHIN1	ENST00000368140.6	c.1360-10530G>A		intron_variant		1	NM_152501.5	ENSP00000357122	P2
PYHIN1	ENST00000368138.7	c.1333-10530G>A		intron_variant		1		ENSP00000357120	A2
PYHIN1	ENST00000392252.7	c.1333-13584G>A		intron_variant		1		ENSP00000376082	A2
PYHIN1	ENST00000392254.6	c.1360-13584G>A		intron_variant		1		ENSP00000376083	A2

Frequencies

GnomAD3 genomes AF: 0.921 AC: 140074 AN: 152020 Hom.: 65630 Cov.: 30

Gnomad AFR AF: 0.728

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.994

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.997

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.943

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

GnomAD4 genome AF: 0.921 AC: 140162 AN: 152138 Hom.: 65664 Cov.: 30 AF XY: 0.924 AC XY: 68720 AN XY: 74370

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.970

Gnomad4 ASJ AF: 0.994

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.998

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.944

Alfa AF: 0.953 Hom.: 8669

Bravo AF: 0.911

Asia WGS AF: 0.977 AC: 3398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.67

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: rs1102000; hg19: chr1-158932907;