rs234494

Positions:

• chrX-15420773-G-A
• chrX-15420773-G-C

Variant summary

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

The NM_001018109.3(PIR):​c.565+5133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 110,365 control chromosomes in the GnomAD database, including 1,850 homozygotes. There are 6,474 hemizygotes in GnomAD. 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 0.19 (1850 hom., 6474 hem., cov: 22)
• Consequence: PIR NM_001018109.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

Genes affected

PIR (HGNC:30048): (pirin) This gene encodes a member of the cupin superfamily. The encoded protein is an Fe(II)-containing nuclear protein expressed in all tissues of the body and concentrated within dot-like subnuclear structures. Interactions with nuclear factor I/CCAAT box transcription factor as well as B cell lymphoma 3-encoded oncoprotein suggest the encoded protein may act as a transcriptional cofactor and be involved in the regulation of DNA transcription and replication. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]

PIR-FIGF (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIR	NM_001018109.3	c.565+5133C>T		intron_variant		ENST00000380420.10	NP_001018119.1
PIR-FIGF	NR_037859.2	n.617+5133C>T		intron_variant, non_coding_transcript_variant
PIR	NM_003662.4	c.565+5133C>T		intron_variant			NP_003653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIR	ENST00000380420.10	c.565+5133C>T		intron_variant		1	NM_001018109.3	ENSP00000369785	P1
PIR	ENST00000380421.3	c.565+5133C>T		intron_variant		1		ENSP00000369786	P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 21466 AN: 110312 Hom.: 1852 Cov.: 22 AF XY: 0.199 AC XY: 6469 AN XY: 32588

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.195 AC: 21467 AN: 110365 Hom.: 1850 Cov.: 22 AF XY: 0.198 AC XY: 6474 AN XY: 32651

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.217

Alfa AF: 0.179 Hom.: 1065

Bravo AF: 0.210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.83

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: rs234494; hg19: chrX-15438896;