rs1131692160

Variant names:

• chr13-72835296-T-TGCTTCGCAGATTGAAAACCAACCAAGAAATTGATCA
• rs1131692160
• NM_006346.4:c.1151_1152insGCTTCGCAGATTGAAAACCAACCAAGAAATTGATCA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_006346.4(PIBF1):​c.1151_1152insGCTTCGCAGATTGAAAACCAACCAAGAAATTGATCA​(p.Ile384delinsMetLeuArgArgLeuLysThrAsnGlnGluIleAspHis) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIBF1 NM_006346.4 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.250
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_006346.4.

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.1151_1152insGCTTCGCAGATTGAAAACCAACCAAGAAATTGATCA	p.Ile384delinsMetLeuArgArgLeuLysThrAsnGlnGluIleAspHis	disruptive_inframe_insertion	Exon 9 of 18	NP_006337.2	Q8WXW3-1
	PIBF1	NM_001349655.2		c.1151_1152insGCTTCGCAGATTGAAAACCAACCAAGAAATTGATCA	p.Ile384delinsMetLeuArgArgLeuLysThrAsnGlnGluIleAspHis	disruptive_inframe_insertion	Exon 9 of 19	NP_001336584.1
	PIBF1	NR_146205.2		n.1438_1439insGCTTCGCAGATTGAAAACCAACCAAGAAATTGATCA		non_coding_transcript_exon	Exon 9 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIBF1	ENST00000326291.11	TSL:1 MANE Select	c.1151_1152insGCTTCGCAGATTGAAAACCAACCAAGAAATTGATCA	p.Ile384delinsMetLeuArgArgLeuLysThrAsnGlnGluIleAspHis	disruptive_inframe_insertion	Exon 9 of 18	ENSP00000317144.6	Q8WXW3-1
	PIBF1	ENST00000617689.4	TSL:1	c.1151_1152insGCTTCGCAGATTGAAAACCAACCAAGAAATTGATCA	p.Ile384delinsMetLeuArgArgLeuLysThrAsnGlnGluIleAspHis	disruptive_inframe_insertion	Exon 9 of 16	ENSP00000478697.1	A0A087WUI6
	PIBF1	ENST00000615625.1	TSL:1	c.-208_-207insGCTTCGCAGATTGAAAACCAACCAAGAAATTGATCA		5_prime_UTR	Exon 2 of 9	ENSP00000483286.1	Q8WXW3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Joubert syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1131692160; hg19: chr13-73409434;