rs10492653

Variant names:

• chr13-72969927-G-A
• rs10492653
• NM_006346.4:c.1965-3664G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-72969927-G-A
• chr13-72969927-G-C

Variant summary

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

The ENST00000326291.11(PIBF1):​c.1965-3664G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,030 control chromosomes in the GnomAD database, including 2,310 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 0.10 (2310 hom., cov: 32)
• Consequence: PIBF1 ENST00000326291.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000326291.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIBF1	NM_006346.4	MANE Select	c.1965-3664G>A		intron	N/A	NP_006337.2
	PIBF1	NM_001349655.2		c.2052-3664G>A		intron	N/A	NP_001336584.1
	PIBF1	NR_146205.2		n.2252-3664G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIBF1	ENST00000326291.11	TSL:1 MANE Select	c.1965-3664G>A		intron	N/A	ENSP00000317144.6
	PIBF1	ENST00000617689.4	TSL:1	c.1965-3664G>A		intron	N/A	ENSP00000478697.1
	PIBF1	ENST00000615625.1	TSL:1	c.342-3664G>A		intron	N/A	ENSP00000483286.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15681 AN: 151912 Hom.: 2301 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.0115

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.0672

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

GnomAD4 genome AF: 0.103 AC: 15713 AN: 152030 Hom.: 2310 Cov.: 32 AF XY: 0.100 AC XY: 7443 AN XY: 74320

African (AFR) AF: 0.329 AC: 13651 AN: 41436

American (AMR) AF: 0.0408 AC: 624 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3472

East Asian (EAS) AF: 0.0214 AC: 111 AN: 5180

South Asian (SAS) AF: 0.0330 AC: 159 AN: 4812

European-Finnish (FIN) AF: 0.0115 AC: 122 AN: 10572

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

European-Non Finnish (NFE) AF: 0.0121 AC: 825 AN: 67970

Other (OTH) AF: 0.0665 AC: 140 AN: 2104

Alfa AF: 0.0424 Hom.: 2175

Bravo AF: 0.115

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.37
PhyloP100		0.10
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: rs10492653; hg19: chr13-73544065;