rs16979877

Variant names:

• chr20-56392982-A-G
• rs16979877
• NM_001324.3:c.-33+269A>G

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+269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 152,096 control chromosomes in the GnomAD database, including 284 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 0.056 (284 hom., cov: 31)
• Consequence: CSTF1 NM_001324.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.456
• Publications: 7 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0804 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSTF1	NM_001324.3	MANE Select	c.-33+269A>G		intron	N/A	NP_001315.1
	CSTF1	NM_001033521.2		c.-33+444A>G		intron	N/A	NP_001028693.1
	CSTF1	NM_001033522.2		c.-33+167A>G		intron	N/A	NP_001028694.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSTF1	ENST00000217109.9	TSL:1 MANE Select	c.-33+269A>G		intron	N/A	ENSP00000217109.4
	CSTF1	ENST00000498689.5	TSL:1	n.168+444A>G		intron	N/A
	CSTF1	ENST00000415828.5	TSL:2	c.-33+444A>G		intron	N/A	ENSP00000387968.1

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8442 AN: 151978 Hom.: 282 Cov.: 31

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.0698

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.0338

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0693

Gnomad OTH AF: 0.0627

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

GnomAD4 genome AF: 0.0556 AC: 8452 AN: 152096 Hom.: 284 Cov.: 31 AF XY: 0.0539 AC XY: 4009 AN XY: 74342

African (AFR) AF: 0.0348 AC: 1446 AN: 41504

American (AMR) AF: 0.0843 AC: 1286 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0698 AC: 242 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5168

South Asian (SAS) AF: 0.0463 AC: 223 AN: 4818

European-Finnish (FIN) AF: 0.0338 AC: 358 AN: 10578

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0693 AC: 4714 AN: 67982

Other (OTH) AF: 0.0620 AC: 131 AN: 2112

Alfa AF: 0.0586 Hom.: 114

Bravo AF: 0.0588

Asia WGS AF: 0.0300 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.26
PhyloP100		0.46
PromoterAI		0.038	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: rs16979877; hg19: chr20-54968038;