chr13-72985844-C-T

Variant names:

• chr13-72985844-C-T
• rs8002688
• NM_006346.4:c.2049+12169C>T

Variant summary

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

The NM_006346.4(PIBF1):​c.2049+12169C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 151,962 control chromosomes in the GnomAD database, including 2,405 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 0.11 (2405 hom., cov: 32)
• Consequence: PIBF1 NM_006346.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 6 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIBF1	NM_006346.4	c.2049+12169C>T		intron_variant	Intron 16 of 17	ENST00000326291.11	NP_006337.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIBF1	ENST00000326291.11	c.2049+12169C>T		intron_variant	Intron 16 of 17	1	NM_006346.4	ENSP00000317144.6
PIBF1	ENST00000615625.1	c.426+12169C>T		intron_variant	Intron 7 of 8	1		ENSP00000483286.1
PIBF1	ENST00000469712.1	n.200+12169C>T		intron_variant	Intron 2 of 3	3
PIBF1	ENST00000489922.5	n.265+12169C>T		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16985 AN: 151846 Hom.: 2396 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0433

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.0361

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0141

Gnomad OTH AF: 0.0696

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

GnomAD4 genome AF: 0.112 AC: 17017 AN: 151962 Hom.: 2405 Cov.: 32 AF XY: 0.113 AC XY: 8422 AN XY: 74290

African (AFR) AF: 0.330 AC: 13667 AN: 41392

American (AMR) AF: 0.0433 AC: 661 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 73 AN: 3472

East Asian (EAS) AF: 0.0311 AC: 160 AN: 5146

South Asian (SAS) AF: 0.0349 AC: 168 AN: 4820

European-Finnish (FIN) AF: 0.111 AC: 1169 AN: 10572

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0142 AC: 962 AN: 67980

Other (OTH) AF: 0.0689 AC: 145 AN: 2104

Alfa AF: 0.0477 Hom.: 1978

Bravo AF: 0.117

Asia WGS AF: 0.0570 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.52
PhyloP100		0.020
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: rs8002688; hg19: chr13-73559982;