rs2737839

Positions:

• chr9-15488818-G-A
• chr9-15488818-G-C
• chr9-15488818-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_033222.5(PSIP1):​c.288+1168C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 152,176 control chromosomes in the GnomAD database, including 20 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 0.016 (20 hom., cov: 32)
• Consequence: PSIP1 NM_033222.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

Genes affected

PSIP1 (HGNC:9527): (PC4 and SRSF1 interacting protein 1) Enables DNA-binding transcription factor binding activity; chromatin binding activity; and transcription coactivator activity. Involved in mRNA 5'-splice site recognition and positive regulation of transcription by RNA polymerase II. Located in heterochromatin; nuclear periphery; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PSIP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0155 (2360/152176) while in subpopulation AFR AF= 0.0345 (1433/41488). AF 95% confidence interval is 0.0331. There are 20 homozygotes in gnomad4. There are 1174 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2360 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSIP1	NM_033222.5	c.288+1168C>T		intron_variant		ENST00000380733.9	NP_150091.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSIP1	ENST00000380733.9	c.288+1168C>T		intron_variant		1	NM_033222.5	ENSP00000370109.4

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2359 AN: 152058 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00954

Gnomad OTH AF: 0.0182

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

GnomAD4 genome AF: 0.0155 AC: 2360 AN: 152176 Hom.: 20 Cov.: 32 AF XY: 0.0158 AC XY: 1174 AN XY: 74402

Gnomad4 AFR AF: 0.0345

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.00283

Gnomad4 NFE AF: 0.00954

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.00259 Hom.: 0

Bravo AF: 0.0172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.97

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

Publications

LitVar

Other links and lift over

dbSNP: rs2737839; hg19: chr9-15488816; COSMIC: COSV66253946; COSMIC: COSV66253946;