Genetic Variant INTS1:c.1911-63C>T (chr7-1493974-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

INTS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080453.3. 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
	INTS1	NM_001080453.3	MANE Select	c.1911-63C>T		intron	N/A	NP_001073922.2	Q8N201

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
INTS1	ENST00000404767.8	TSL:5 MANE Select	c.1911-63C>T	intron	N/A	ENSP00000385722.3	Q8N201
INTS1	ENST00000951930.1		c.1911-63C>T	intron	N/A	ENSP00000621989.1
INTS1	ENST00000916004.1		c.1911-63C>T	intron	N/A	ENSP00000586063.1

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

African (AFR)

AF:

0.00529

AC:

160

AN:

30246

American (AMR)

AF:

0.0537

AC:

1731

AN:

32256

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

454

AN:

22804

East Asian (EAS)

AF:

0.137

AC:

4787

AN:

34820

South Asian (SAS)

AF:

0.0720

AC:

5287

AN:

73472

European-Finnish (FIN)

AF:

0.0502

AC:

2353

AN:

46898

Middle Eastern (MID)

AF:

0.0539

AC:

271

AN:

5032

European-Non Finnish (NFE)

AF:

0.0250

AC:

26234

AN:

1049376

Other (OTH)

AF:

0.0392

AC:

2187

AN:

55744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1837

3675

5512

7350

9187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1090

2180

3270

4360

5450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0328

AC:

5001

AN:

152280

Hom.:

189

Cov.:

AF XY:

0.0362

AC XY:

2699

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00527

AC:

219

AN:

41580

American (AMR)

AF:

0.0565

AC:

865

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

AN:

3470

East Asian (EAS)

AF:

0.158

AC:

813

AN:

5158

South Asian (SAS)

AF:

0.0742

AC:

358

AN:

4824

European-Finnish (FIN)

AF:

0.0575

AC:

611

AN:

10622

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0277

AC:

1887

AN:

68002

Other (OTH)

AF:

0.0388

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

242

485

727

970

1212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.0

(source)

DANN

Benign

0.80

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over