dbSNP rs201688337: INTS11:p.Arg529Arg (chr1-1312246-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

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

The NM_017871.6(INTS11):c.1587C>T(p.Arg529Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,534,260 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 13 hom. )

Consequence

INTS11
NM_017871.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.77

Variant links:

Genes affected

INTS11 (HGNC:26052): (integrator complex subunit 11) The Integrator complex contains at least 12 subunits and associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates the 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690). INTS11, or CPSF3L, is the catalytic subunit of the Integrator complex (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

INTS11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 1-1312246-G-A is Benign according to our data. Variant chr1-1312246-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3770602.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.77 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS11	NM_017871.6 link	c.1587C>T	p.Arg529Arg	synonymous_variant	Exon 15 of 17	ENST00000435064.6	NP_060341.2	Q5TA45-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS11	ENST00000435064.6 link	c.1587C>T	p.Arg529Arg	synonymous_variant	Exon 15 of 17	1	NM_017871.6	ENSP00000413493.2		Q5TA45-1

Frequencies

GnomAD3 genomes

AF:

0.00166

AC:

245

AN:

147626

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000588

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00139

Gnomad ASJ

AF:

0.00204

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000845

Gnomad FIN

AF:

0.000555

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00270

Gnomad OTH

AF:

0.00199

GnomAD3 exomes

AF:

0.00177

AC:

267

AN:

150456

Hom.:

AF XY:

0.00173

AC XY:

139

AN XY:

80130

show subpopulations

Gnomad AFR exome

AF:

0.000116

Gnomad AMR exome

AF:

0.00219

Gnomad ASJ exome

AF:

0.00227

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.00271

Gnomad OTH exome

AF:

0.00257

GnomAD4 exome

AF:

0.00253

AC:

3513

AN:

1386512

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

1723

AN XY:

682396

show subpopulations

Gnomad4 AFR exome

AF:

0.000470

Gnomad4 AMR exome

AF:

0.00221

Gnomad4 ASJ exome

AF:

0.00196

Gnomad4 EAS exome

AF:

0.0000827

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.00137

Gnomad4 NFE exome

AF:

0.00288

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.00166

AC:

245

AN:

147748

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

101

AN XY:

71272

show subpopulations

Gnomad4 AFR

AF:

0.000586

Gnomad4 AMR

AF:

0.00139

Gnomad4 ASJ

AF:

0.00204

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000847

Gnomad4 FIN

AF:

0.000555

Gnomad4 NFE

AF:

0.00270

Gnomad4 OTH

AF:

0.00197

Alfa

AF:

0.00217

Hom.:

Bravo

AF:

0.00194

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

INTS11: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.15

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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