20-56393679-G-T

Variant names:

• chr20-56393679-G-T
• rs6064389
• NM_001324.3:c.-33+966G>T

Variant summary

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

The NM_001324.3(CSTF1):​c.-33+966G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 148,252 control chromosomes in the GnomAD database, including 14,845 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 0.43 (14845 hom., cov: 27)
• Consequence: CSTF1 NM_001324.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524
• Publications: 14 publications found

Genes affected

CSTF1 (HGNC:2483): (cleavage stimulation factor subunit 1) This gene encodes one of three subunits which combine to form cleavage stimulation factor (CSTF). CSTF is involved in the polyadenylation and 3'end cleavage of pre-mRNAs. Similar to mammalian G protein beta subunits, this protein contains transducin-like repeats. Several transcript variants with different 5' UTR, but encoding the same protein, have been found for this gene. [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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001324.3. 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
	CSTF1	NM_001324.3	MANE Select	c.-33+966G>T		intron	N/A	NP_001315.1	Q05048
	CSTF1	NM_001033521.2		c.-33+1141G>T		intron	N/A	NP_001028693.1	Q05048
	CSTF1	NM_001033522.2		c.-33+864G>T		intron	N/A	NP_001028694.1	Q05048

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSTF1	ENST00000217109.9	TSL:1 MANE Select	c.-33+966G>T		intron	N/A	ENSP00000217109.4	Q05048
	CSTF1	ENST00000498689.5	TSL:1	n.168+1141G>T		intron	N/A
	CSTF1	ENST00000892724.1		c.-1874G>T		5_prime_UTR	Exon 1 of 5	ENSP00000562783.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 64123 AN: 148128 Hom.: 14850 Cov.: 27

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.433 AC: 64129 AN: 148252 Hom.: 14845 Cov.: 27 AF XY: 0.437 AC XY: 31418 AN XY: 71960

African (AFR) AF: 0.305 AC: 12414 AN: 40660

American (AMR) AF: 0.486 AC: 7156 AN: 14714

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1459 AN: 3458

East Asian (EAS) AF: 0.845 AC: 4041 AN: 4784

South Asian (SAS) AF: 0.474 AC: 2178 AN: 4598

European-Finnish (FIN) AF: 0.512 AC: 4775 AN: 9322

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30669 AN: 67444

Other (OTH) AF: 0.437 AC: 910 AN: 2082

Alfa AF: 0.452 Hom.: 9411

Bravo AF: 0.435

Asia WGS AF: 0.608 AC: 2111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.7
DANN	Benign	0.53
PhyloP100		0.52
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: rs6064389; hg19: chr20-54968735;