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, Ambry Genetics, Labcorp Genetics (formerly Invitae)

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
INTS1	NM_001080453.3 link	c.1911-63C>T	intron_variant	Intron 14 of 47	ENST00000404767.8	NP_001073922.2	Q8N201
INTS1	XM_011515260.2 link	c.1911-63C>T	intron_variant	Intron 14 of 47		XP_011513562.1
INTS1	XM_011515262.3 link	c.1911-63C>T	intron_variant	Intron 14 of 27		XP_011513564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS1	ENST00000404767.8 link	c.1911-63C>T		intron_variant	Intron 14 of 47	5	NM_001080453.3	ENSP00000385722.3		Q8N201
INTS1	ENST00000468115.1 link	n.-107C>T		upstream_gene_variant		2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over