rs2277191

Variant names:

• chr9-15510591-G-A
• rs2277191
• NM_033222.5:c.-142+226C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-15510591-G-A
• chr9-15510591-G-C

Variant summary

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

The NM_033222.5(PSIP1):​c.-142+226C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 152,064 control chromosomes in the GnomAD database, including 191 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 0.038 (191 hom., cov: 32)
• Consequence: PSIP1 NM_033222.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSIP1	NM_033222.5	c.-142+226C>T		intron_variant	Intron 1 of 15	ENST00000380733.9	NP_150091.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSIP1	ENST00000380733.9	c.-142+226C>T		intron_variant	Intron 1 of 15	1	NM_033222.5	ENSP00000370109.4

Frequencies

GnomAD3 genomes AF: 0.0378 AC: 5749 AN: 151954 Hom.: 187 Cov.: 32

Gnomad AFR AF: 0.0790

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.0939

Gnomad SAS AF: 0.0714

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.0345

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

GnomAD4 genome AF: 0.0379 AC: 5769 AN: 152064 Hom.: 191 Cov.: 32 AF XY: 0.0389 AC XY: 2889 AN XY: 74326

African (AFR) AF: 0.0791 AC: 3282 AN: 41476

American (AMR) AF: 0.0322 AC: 493 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3470

East Asian (EAS) AF: 0.0936 AC: 481 AN: 5140

South Asian (SAS) AF: 0.0712 AC: 343 AN: 4816

European-Finnish (FIN) AF: 0.0156 AC: 165 AN: 10586

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0113 AC: 765 AN: 67970

Other (OTH) AF: 0.0384 AC: 81 AN: 2110

Alfa AF: 0.00376 Hom.: 0

Bravo AF: 0.0396

Asia WGS AF: 0.0900 AC: 311 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.8
DANN	Benign	0.80
PhyloP100		-0.046
PromoterAI		-0.011	Neutral
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: rs2277191; hg19: chr9-15510589;