NM_006346.4:c.252+1833C>G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006346.4(PIBF1):​c.252+1833C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006346.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIBF1	NM_006346.4	MANE Select	c.252+1833C>G		intron	N/A	NP_006337.2	Q8WXW3-1
	PIBF1	NM_001349655.2		c.252+1833C>G		intron	N/A	NP_001336584.1
	PIBF1	NR_146205.2		n.516+1833C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIBF1	ENST00000326291.11	TSL:1 MANE Select	c.252+1833C>G		intron	N/A	ENSP00000317144.6	Q8WXW3-1
	PIBF1	ENST00000617689.4	TSL:1	c.252+1833C>G		intron	N/A	ENSP00000478697.1	A0A087WUI6
	PIBF1	ENST00000615625.1	TSL:1	c.-262+3205C>G		intron	N/A	ENSP00000483286.1	Q8WXW3-2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.61
PhyloP100		-1.9

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;