rs425468

Positions:

• chr11-33124082-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CSTF3	NM_001326.3	c.226-15664T>C		intron_variant		ENST00000323959.9	NP_001317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSTF3	ENST00000323959.9	c.226-15664T>C		intron_variant		1	NM_001326.3	ENSP00000315791	P1
CSTF3	ENST00000524827.6	c.322-15664T>C		intron_variant		3		ENSP00000431355

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

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.587

Alfa AF: 0.627 Hom.: 3979

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

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: rs425468; hg19: chr11-33145628;