rs16979877

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSTF1	NM_001324.3	c.-33+269A>G		intron_variant	Intron 1 of 5	ENST00000217109.9	NP_001315.1
CSTF1	NM_001033521.2	c.-33+444A>G		intron_variant	Intron 1 of 5		NP_001028693.1
CSTF1	NM_001033522.2	c.-33+167A>G		intron_variant	Intron 1 of 5		NP_001028694.1
CSTF1	XM_011528600.2	c.-33+243A>G		intron_variant	Intron 1 of 5		XP_011526902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSTF1	ENST00000217109.9	c.-33+269A>G		intron_variant	Intron 1 of 5	1	NM_001324.3	ENSP00000217109.4

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

Gnomad4 AFR AF: 0.0348

Gnomad4 AMR AF: 0.0843

Gnomad4 ASJ AF: 0.0698

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0463

Gnomad4 FIN AF: 0.0338

Gnomad4 NFE AF: 0.0693

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0601 Hom.: 65

Bravo AF: 0.0588

Asia WGS AF: 0.0300 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.26

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: rs16979877; hg19: chr20-54968038;