Variant rs2304356 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001080453.3(INTS1):c.1911-63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 1,502,928 control chromosomes in the GnomAD database, including 1,360 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.033 ( 189 hom., cov: 33)

Exomes 𝑓: 0.032 ( 1171 hom. )

Consequence

INTS1
NM_001080453.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.46

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
INTS1	NM_001080453.3 linkuse as main transcript	c.1911-63C>T	intron_variant	ENST00000404767.8	NP_001073922.2
INTS1	XM_011515260.2 linkuse as main transcript	c.1911-63C>T	intron_variant		XP_011513562.1
INTS1	XM_011515262.3 linkuse as main transcript	c.1911-63C>T	intron_variant		XP_011513564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS1	ENST00000404767.8 linkuse as main transcript	c.1911-63C>T		intron_variant		5	NM_001080453.3	ENSP00000385722	P1

Frequencies

GnomAD3 genomes

AF:

0.0329

AC:

5009

AN:

152162

Hom.:

190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00528

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.0568

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.0739

Gnomad FIN

AF:

0.0575

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0277

Gnomad OTH

AF:

0.0397

GnomAD4 exome

AF:

0.0322

AC:

43464

AN:

1350648

Hom.:

1171

AF XY:

0.0334

AC XY:

22059

AN XY:

660746

show subpopulations

Gnomad4 AFR exome

AF:

0.00529

Gnomad4 AMR exome

AF:

0.0537

Gnomad4 ASJ exome

AF:

0.0199

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.0720

Gnomad4 FIN exome

AF:

0.0502

Gnomad4 NFE exome

AF:

0.0250

Gnomad4 OTH exome

AF:

0.0392

GnomAD4 genome

AF:

0.0328

AC:

5001

AN:

152280

Hom.:

189

Cov.:

AF XY:

0.0362

AC XY:

2699

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00527

Gnomad4 AMR

AF:

0.0565

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.158

Gnomad4 SAS

AF:

0.0742

Gnomad4 FIN

AF:

0.0575

Gnomad4 NFE

AF:

0.0277

Gnomad4 OTH

AF:

0.0388

Alfa

AF:

0.0161

Hom.:

Bravo

AF:

0.0315

Asia WGS

AF:

0.0950

AC:

329

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.0

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over