chr9-113275672-C-T

Variant names:

• chr9-113275672-C-T
• rs377499486
• NM_001244926.2:c.-72C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_001244926.2(PRPF4):​c.-72C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,550,452 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (1 hom.)
• Consequence: PRPF4 NM_001244926.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.30
• Publications: 1 publications found

Genes affected

PRPF4 (HGNC:17349): (pre-mRNA splicing tri-snRNP complex factor PRPF4) The protein encoded by this gene is part of a heteromeric complex that binds U4, U5, and U6 small nuclear RNAs and is involved in pre-mRNA splicing. The encoded protein also is a mitotic checkpoint protein and a regulator of chemoresistance in human ovarian cancer. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2016]

CDC26 (HGNC:17839): (cell division cycle 26) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc26, a component of cell cycle anaphase-promoting complex (APC). APC is composed of a group of highly conserved proteins and functions as a cell cycle-regulated ubiquitin-protein ligase. APC thus is responsible for the cell cycle regulated proteolysis of various proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 9-113275672-C-T is Benign according to our data. Variant chr9-113275672-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3042380.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 166 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244926.2. 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
	PRPF4	NM_001244926.2	MANE Select	c.-72C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	NP_001231855.1	O43172-2
	PRPF4	NM_001244926.2	MANE Select	c.-72C>T		5_prime_UTR	Exon 1 of 14	NP_001231855.1	O43172-2
	PRPF4	NM_004697.5		c.-72C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	NP_004688.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF4	ENST00000374198.5	TSL:1 MANE Select	c.-72C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	ENSP00000363313.4	O43172-2
	PRPF4	ENST00000374199.9	TSL:1	c.-72C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	ENSP00000363315.4	O43172-1
	PRPF4	ENST00000374198.5	TSL:1 MANE Select	c.-72C>T		5_prime_UTR	Exon 1 of 14	ENSP00000363313.4	O43172-2

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 166 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00179

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00166 AC: 2322 AN: 1398128 Hom.: 1 Cov.: 26 AF XY: 0.00154 AC XY: 1068 AN XY: 692342

African (AFR) AF: 0.000319 AC: 10 AN: 31388

American (AMR) AF: 0.00160 AC: 63 AN: 39274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23304

East Asian (EAS) AF: 0.00 AC: 0 AN: 37314

South Asian (SAS) AF: 0.0000373 AC: 3 AN: 80342

European-Finnish (FIN) AF: 0.0000403 AC: 2 AN: 49584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5494

European-Non Finnish (NFE) AF: 0.00198 AC: 2127 AN: 1073810

Other (OTH) AF: 0.00203 AC: 117 AN: 57618

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152324 Hom.: 1 Cov.: 32 AF XY: 0.000993 AC XY: 74 AN XY: 74492

African (AFR) AF: 0.000168 AC: 7 AN: 41576

American (AMR) AF: 0.00209 AC: 32 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00179 AC: 122 AN: 68018

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00121

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PRPF4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		1.3
PromoterAI		-0.065	Neutral
Mutation Taster		=299/1	polymorphism

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: rs377499486; hg19: chr9-116037952; COSMIC: COSV104684050; COSMIC: COSV104684050;