Genetic Variant CSTF2:p.Pro380Pro (chrX-100832842-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001325.3(CSTF2):c.1140C>T(p.Pro380Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00428 in 1,207,897 control chromosomes in the GnomAD database, including 146 homozygotes. There are 1,383 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 69 hom., 673 hem., cov: 22)

Exomes 𝑓: 0.0025 ( 77 hom. 710 hem. )

Consequence

CSTF2
NM_001325.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0420

Variant links:

Genes affected

CSTF2 (HGNC:2484): (cleavage stimulation factor subunit 2) This gene encodes a nuclear protein with an RRM (RNA recognition motif) domain. The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3' end cleavage and polyadenylation of pre-mRNAs. Specifically, this protein binds GU-rich elements within the 3'-untranslated region of mRNAs. [provided by RefSeq, Jul 2008]

CSTF2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant X-100832842-C-T is Benign according to our data. Variant chrX-100832842-C-T is described in ClinVar as [Benign]. Clinvar id is 781552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.042 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSTF2	NM_001325.3 link	c.1140C>T	p.Pro380Pro	synonymous_variant	Exon 10 of 14	ENST00000372972.7	NP_001316.1	P33240-1
CSTF2	NM_001306206.2 link	c.1200C>T	p.Pro400Pro	synonymous_variant	Exon 11 of 15		NP_001293135.1	E7EWR4B3V096B4DUD5
CSTF2	NM_001306209.2 link	c.1089C>T	p.Pro363Pro	synonymous_variant	Exon 10 of 14		NP_001293138.1	P33240-2B4DUD5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CSTF2	ENST00000372972.7 link	c.1140C>T	p.Pro380Pro	synonymous_variant	Exon 10 of 14	1	NM_001325.3	ENSP00000362063.2	P33240-1
CSTF2	ENST00000415585.7 link	c.1200C>T	p.Pro400Pro	synonymous_variant	Exon 11 of 15	1		ENSP00000387996.2	E7EWR4
CSTF2	ENST00000475126.5 link	n.1089C>T		non_coding_transcript_exon_variant	Exon 10 of 14	5		ENSP00000432060.1	E9PID8

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

2449

AN:

111873

Hom.:

Cov.:

AF XY:

0.0195

AC XY:

664

AN XY:

34085

show subpopulations

Gnomad AFR

AF:

0.0752

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00914

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00840

Gnomad NFE

AF:

0.000414

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00635

AC:

1119

AN:

176296

Hom.:

AF XY:

0.00388

AC XY:

238

AN XY:

61282

show subpopulations

Gnomad AFR exome

AF:

0.0784

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000738

Gnomad SAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000192

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00247

AC:

2706

AN:

1095972

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

710

AN XY:

361464

show subpopulations

Gnomad4 AFR exome

AF:

0.0793

Gnomad4 AMR exome

AF:

0.00482

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000149

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000163

Gnomad4 OTH exome

AF:

0.00606

GnomAD4 genome

AF:

0.0220

AC:

2466

AN:

111925

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

673

AN XY:

34147

show subpopulations

Gnomad4 AFR

AF:

0.0756

Gnomad4 AMR

AF:

0.00913

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000414

Gnomad4 OTH

AF:

0.0138

Alfa

AF:

0.00852

Hom.:

Bravo

AF:

0.0251

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.5

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over