Variant 4-105682913-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020395.4(INTS12):c.1209G>A(p.Gly403=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 1,614,062 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 17 hom. )

Consequence

INTS12
NM_020395.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.14

Variant links:

Genes affected

INTS12 (HGNC:25067): (integrator complex subunit 12) INTS12 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

INTS12 links:

ARHGEF38 (HGNC:25968): (Rho guanine nucleotide exchange factor 38) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ARHGEF38 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=-0.6).

BP6

Variant 4-105682913-C-T is Benign according to our data. Variant chr4-105682913-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2655003.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.14 with no splicing effect.

BS2

High AC in GnomAd4 at 406 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS12	NM_020395.4 linkuse as main transcript	c.1209G>A	p.Gly403=	synonymous_variant	8/8	ENST00000340139.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
INTS12	ENST00000340139.10 linkuse as main transcript	c.1209G>A	p.Gly403=	synonymous_variant	8/8	1	NM_020395.4	P1
INTS12	ENST00000451321.6 linkuse as main transcript	c.1209G>A	p.Gly403=	synonymous_variant	7/7	1		P1
INTS12	ENST00000394735.5 linkuse as main transcript	c.1209G>A	p.Gly403=	synonymous_variant	8/8	5		P1
ARHGEF38	ENST00000503289.1 linkuse as main transcript	n.308-9C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00267

AC:

406

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00445

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00292

AC:

734

AN:

251434

Hom.:

AF XY:

0.00308

AC XY:

418

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.0115

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00152

Gnomad NFE exome

AF:

0.00440

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00439

AC:

6412

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

3106

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000997

Gnomad4 FIN exome

AF:

0.00161

Gnomad4 NFE exome

AF:

0.00506

Gnomad4 OTH exome

AF:

0.00449

GnomAD4 genome

AF:

0.00267

AC:

406

AN:

152252

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

181

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00446

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00413

Hom.:

Bravo

AF:

0.00241

Asia WGS

AF:

0.000866

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

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

INTS12: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.8

DANN

Benign

0.49

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