X-100822260-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001325.3(CSTF2):​c.147C>T​(p.Tyr49Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000249 in 1,207,129 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.000023 ( 0 hom. 8 hem. )

Consequence

CSTF2
NM_001325.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.90
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant X-100822260-C-T is Benign according to our data. Variant chrX-100822260-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 745214.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.9 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSTF2NM_001325.3 linkc.147C>T p.Tyr49Tyr synonymous_variant Exon 3 of 14 ENST00000372972.7 NP_001316.1 P33240-1
CSTF2NM_001306206.2 linkc.147C>T p.Tyr49Tyr synonymous_variant Exon 3 of 15 NP_001293135.1 E7EWR4B3V096B4DUD5
CSTF2NM_001306209.2 linkc.147C>T p.Tyr49Tyr synonymous_variant Exon 3 of 14 NP_001293138.1 P33240-2B4DUD5
CSTF2XM_047441854.1 linkc.147C>T p.Tyr49Tyr synonymous_variant Exon 3 of 10 XP_047297810.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSTF2ENST00000372972.7 linkc.147C>T p.Tyr49Tyr synonymous_variant Exon 3 of 14 1 NM_001325.3 ENSP00000362063.2 P33240-1
CSTF2ENST00000415585.7 linkc.147C>T p.Tyr49Tyr synonymous_variant Exon 3 of 15 1 ENSP00000387996.2 E7EWR4
CSTF2ENST00000413437.1 linkc.120C>T p.Tyr40Tyr synonymous_variant Exon 3 of 6 5 ENSP00000415705.1 A0A0A0MT56
CSTF2ENST00000475126.5 linkn.147C>T non_coding_transcript_exon_variant Exon 3 of 14 5 ENSP00000432060.1 E9PID8

Frequencies

GnomAD3 genomes
AF:
0.0000449
AC:
5
AN:
111441
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33641
show subpopulations
Gnomad AFR
AF:
0.0000980
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000951
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000165
AC:
3
AN:
181447
Hom.:
0
AF XY:
0.0000152
AC XY:
1
AN XY:
65981
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000735
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000123
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000228
AC:
25
AN:
1095688
Hom.:
0
Cov.:
29
AF XY:
0.0000222
AC XY:
8
AN XY:
361138
show subpopulations
Gnomad4 AFR exome
AF:
0.0000380
Gnomad4 AMR exome
AF:
0.0000569
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000331
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000214
Gnomad4 OTH exome
AF:
0.0000652
GnomAD4 genome
AF:
0.0000449
AC:
5
AN:
111441
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33641
show subpopulations
Gnomad4 AFR
AF:
0.0000980
Gnomad4 AMR
AF:
0.0000951
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000680

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jun 08, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
CADD
Benign
7.6
DANN
Benign
0.71

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.

Other links and lift over

dbSNP: rs766161610; hg19: chrX-100077249; COSMIC: COSV63376249; COSMIC: COSV63376249; API