rs425468

Variant names:

• chr11-33124082-A-G
• rs425468
• NM_001326.3:c.226-15664T>C

Variant summary

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

The NM_001326.3(CSTF3):​c.226-15664T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,974 control chromosomes in the GnomAD database, including 26,084 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 0.56 (26084 hom., cov: 31)
• Consequence: CSTF3 NM_001326.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556
• Publications: 1 publications found

Genes affected

CSTF3 (HGNC:2485): (cleavage stimulation factor subunit 3) The protein encoded by this gene is one of three (including CSTF1 and CSTF2) cleavage stimulation factors that combine to form the cleavage stimulation factor complex (CSTF). This complex is involved in the polyadenylation and 3' end cleavage of pre-mRNAs. The encoded protein functions as a homodimer and interacts directly with both CSTF1 and CSTF2 in the CSTF complex. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSTF3	NM_001326.3	c.226-15664T>C		intron_variant	Intron 3 of 20	ENST00000323959.9	NP_001317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSTF3	ENST00000323959.9	c.226-15664T>C		intron_variant	Intron 3 of 20	1	NM_001326.3	ENSP00000315791.4
CSTF3	ENST00000524827.6	c.322-15664T>C		intron_variant	Intron 4 of 21	3		ENSP00000431355.2

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84430 AN: 151856 Hom.: 26072 Cov.: 31

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.556 AC: 84473 AN: 151974 Hom.: 26084 Cov.: 31 AF XY: 0.559 AC XY: 41499 AN XY: 74280

African (AFR) AF: 0.263 AC: 10907 AN: 41510

American (AMR) AF: 0.612 AC: 9354 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2114 AN: 3468

East Asian (EAS) AF: 0.589 AC: 3053 AN: 5186

South Asian (SAS) AF: 0.621 AC: 2994 AN: 4822

European-Finnish (FIN) AF: 0.674 AC: 7100 AN: 10532

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 46993 AN: 67868

Other (OTH) AF: 0.587 AC: 1237 AN: 2108

Alfa AF: 0.613 Hom.: 4012

Bravo AF: 0.537

Asia WGS AF: 0.601 AC: 2076 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.5
DANN	Benign	0.86
PhyloP100		0.56
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: rs425468; hg19: chr11-33145628;