Variant 7-1471198-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001080453.3(INTS1):c.6282G>A(p.Ser2094=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,581,728 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 16 hom. )

Consequence

INTS1
NM_001080453.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.56

Variant links:

Genes affected

INTS1 (HGNC:24555): (integrator complex subunit 1) INTS1 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]

INTS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 7-1471198-C-T is Benign according to our data. Variant chr7-1471198-C-T is described in ClinVar as [Benign]. Clinvar id is 789292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.56 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00157 (239/152360) while in subpopulation SAS AF= 0.0139 (67/4834). AF 95% confidence interval is 0.0112. There are 1 homozygotes in gnomad4. There are 145 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS1	NM_001080453.3 linkuse as main transcript	c.6282G>A	p.Ser2094=	synonymous_variant	46/48	ENST00000404767.8
INTS1	XM_011515260.2 linkuse as main transcript	c.6312G>A	p.Ser2104=	synonymous_variant	46/48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
INTS1	ENST00000404767.8 linkuse as main transcript	c.6282G>A	p.Ser2094=	synonymous_variant	46/48	5	NM_001080453.3	P1
INTS1	ENST00000483196.1 linkuse as main transcript	c.321G>A	p.Ser107=	synonymous_variant	4/4	5
INTS1	ENST00000479671.1 linkuse as main transcript	n.218G>A		non_coding_transcript_exon_variant	2/2	2
INTS1	ENST00000493446.1 linkuse as main transcript	n.266G>A		non_coding_transcript_exon_variant	4/6	3

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

241

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00280

AC:

539

AN:

192728

Hom.:

AF XY:

0.00352

AC XY:

367

AN XY:

104180

show subpopulations

Gnomad AFR exome

AF:

0.0000952

Gnomad AMR exome

AF:

0.00192

Gnomad ASJ exome

AF:

0.0127

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00928

Gnomad FIN exome

AF:

0.0000594

Gnomad NFE exome

AF:

0.00141

Gnomad OTH exome

AF:

0.00361

GnomAD4 exome

AF:

0.00155

AC:

2209

AN:

1429368

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

1363

AN XY:

707886

show subpopulations

Gnomad4 AFR exome

AF:

0.000336

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00943

Gnomad4 FIN exome

AF:

0.0000608

Gnomad4 NFE exome

AF:

0.000745

Gnomad4 OTH exome

AF:

0.00257

GnomAD4 genome

AF:

0.00157

AC:

239

AN:

152360

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

145

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00197

Hom.:

Bravo

AF:

0.00146

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	INTS1: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.095

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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