rs61741775

Variant names:

• chrX-100832842-C-T
• rs61741775
• NM_001325.3:c.1140C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0420
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, X-linked 113

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001325.3. 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
	CSTF2	NM_001325.3	MANE Select	c.1140C>T	p.Pro380Pro	synonymous	Exon 10 of 14	NP_001316.1	P33240-1
	CSTF2	NM_001306206.2		c.1200C>T	p.Pro400Pro	synonymous	Exon 11 of 15	NP_001293135.1	E7EWR4
	CSTF2	NM_001306209.2		c.1089C>T	p.Pro363Pro	synonymous	Exon 10 of 14	NP_001293138.1	P33240-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSTF2	ENST00000372972.7	TSL:1 MANE Select	c.1140C>T	p.Pro380Pro	synonymous	Exon 10 of 14	ENSP00000362063.2	P33240-1
	CSTF2	ENST00000415585.7	TSL:1	c.1200C>T	p.Pro400Pro	synonymous	Exon 11 of 15	ENSP00000387996.2	E7EWR4
	CSTF2	ENST00000866722.1		c.1287C>T	p.Pro429Pro	synonymous	Exon 12 of 16	ENSP00000536781.1

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 2449 AN: 111873 Hom.: 66 Cov.: 22

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

GnomAD2 exomes AF: 0.00635 AC: 1119 AN: 176296 AF XY: 0.00388

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 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.: 77 Cov.: 31 AF XY: 0.00196 AC XY: 710 AN XY: 361464

African (AFR) AF: 0.0793 AC: 2091 AN: 26374

American (AMR) AF: 0.00482 AC: 169 AN: 35047

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19352

East Asian (EAS) AF: 0.00 AC: 0 AN: 30162

South Asian (SAS) AF: 0.000149 AC: 8 AN: 53574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40404

Middle Eastern (MID) AF: 0.00532 AC: 22 AN: 4134

European-Non Finnish (NFE) AF: 0.000163 AC: 137 AN: 840902

Other (OTH) AF: 0.00606 AC: 279 AN: 46023

GnomAD4 genome AF: 0.0220 AC: 2466 AN: 111925 Hom.: 69 Cov.: 22 AF XY: 0.0197 AC XY: 673 AN XY: 34147

African (AFR) AF: 0.0756 AC: 2324 AN: 30732

American (AMR) AF: 0.00913 AC: 97 AN: 10629

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3545

South Asian (SAS) AF: 0.00 AC: 0 AN: 2669

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6150

Middle Eastern (MID) AF: 0.00922 AC: 2 AN: 217

European-Non Finnish (NFE) AF: 0.000414 AC: 22 AN: 53125

Other (OTH) AF: 0.0138 AC: 21 AN: 1526

Alfa AF: 0.00852 Hom.: 76

Bravo AF: 0.0251

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.5
DANN	Benign	0.58
PhyloP100		-0.042
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: rs61741775; hg19: chrX-100087831;