chr13-72785554-C-A

Variant names:

• chr13-72785554-C-A
• rs7321718
• NM_006346.4:c.252+1833C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006346.4(PIBF1):​c.252+1833C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,050 control chromosomes in the GnomAD database, including 27,330 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 0.59 (27330 hom., cov: 32)
• Consequence: PIBF1 NM_006346.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 1 publications found

Genes affected

PIBF1 (HGNC:23352): (progesterone immunomodulatory binding factor 1) This gene encodes a protein that is induced by the steroid hormone progesterone and plays a role in the maintenance of pregnancy. The encoded protein regulates multiple facets of the immune system to promote normal pregnancy including cytokine synthesis, natural killer (NK) cell activity, and arachidonic acid metabolism. Low serum levels of this protein have been associated with spontaneous pre-term labor in humans. This protein may promote the proliferation, migration and invasion of glioma. [provided by RefSeq, Mar 2017]

PIBF1 Gene-Disease associations (from GenCC):

• Joubert syndrome 33

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• ciliopathy

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIBF1	NM_006346.4	c.252+1833C>A		intron_variant	Intron 2 of 17	ENST00000326291.11	NP_006337.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIBF1	ENST00000326291.11	c.252+1833C>A		intron_variant	Intron 2 of 17	1	NM_006346.4	ENSP00000317144.6
PIBF1	ENST00000617689.4	c.252+1833C>A		intron_variant	Intron 2 of 15	1		ENSP00000478697.1
PIBF1	ENST00000615625.1	c.-262+3205C>A		intron_variant	Intron 1 of 8	1		ENSP00000483286.1
PIBF1	ENST00000489797.1	n.196+3205C>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90059 AN: 151932 Hom.: 27307 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.593 AC: 90137 AN: 152050 Hom.: 27330 Cov.: 32 AF XY: 0.596 AC XY: 44260 AN XY: 74312

African (AFR) AF: 0.678 AC: 28117 AN: 41466

American (AMR) AF: 0.655 AC: 10018 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1836 AN: 3468

East Asian (EAS) AF: 0.758 AC: 3921 AN: 5172

South Asian (SAS) AF: 0.723 AC: 3487 AN: 4822

European-Finnish (FIN) AF: 0.494 AC: 5225 AN: 10570

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35810 AN: 67946

Other (OTH) AF: 0.565 AC: 1194 AN: 2112

Alfa AF: 0.559 Hom.: 4919

Bravo AF: 0.609

Asia WGS AF: 0.712 AC: 2474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.54
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7321718; hg19: chr13-73359692;