Genetic Variant INTS3:c.2552+108G>A (chr1-153770841-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_023015.5(INTS3):c.2552+108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 849,526 control chromosomes in the GnomAD database, including 80,353 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 0.41 ( 12846 hom., cov: 32)

Exomes 𝑓: 0.44 ( 67507 hom. )

Consequence

INTS3
NM_023015.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.191

Publications

8 publications found

Variant links:

Genes affected

INTS3 (HGNC:26153): (integrator complex subunit 3) The protein encoded by this gene can form a complex with human single-strand DNA binding proteins 1 or 2 (hSSB1 and hSSB2) and other proteins to mediate genome stability and the DNA damage response. The encoded protein is also part of a multiprotein complex that interacts with the C-terminal domain of RNA polymerase II large subunit to help regulate processing of U1 and U2 small nuclear RNAs. [provided by RefSeq, May 2016]

INTS3 links:

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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=-0.7).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023015.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS3	NM_023015.5	MANE Select	c.2552+108G>A		intron	N/A	NP_075391.3
	INTS3	NM_001324475.2		c.2552+108G>A		intron	N/A	NP_001311404.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
INTS3	ENST00000318967.7	TSL:1 MANE Select	c.2552+108G>A	intron	N/A	ENSP00000318641.2
INTS3	ENST00000476843.5	TSL:1	n.*1175+108G>A	intron	N/A	ENSP00000485263.1
INTS3	ENST00000435409.6	TSL:2	c.2552+108G>A	intron	N/A	ENSP00000404290.2

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61932

AN:

151878

Hom.:

12841

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.498

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.464

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.426

Gnomad OTH

AF:

0.423

GnomAD4 exome

AF:

0.436

AC:

304394

AN:

697530

Hom.:

67507

AF XY:

0.440

AC XY:

162436

AN XY:

369504

show subpopulations

African (AFR)

AF:

0.384

AC:

7040

AN:

18326

American (AMR)

AF:

0.444

AC:

15855

AN:

35744

Ashkenazi Jewish (ASJ)

AF:

0.515

AC:

10576

AN:

20540

East Asian (EAS)

AF:

0.255

AC:

8478

AN:

33290

South Asian (SAS)

AF:

0.489

AC:

32536

AN:

66550

European-Finnish (FIN)

AF:

0.393

AC:

16368

AN:

41684

Middle Eastern (MID)

AF:

0.549

AC:

2369

AN:

4318

European-Non Finnish (NFE)

AF:

0.443

AC:

195786

AN:

441810

Other (OTH)

AF:

0.436

AC:

15386

AN:

35268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

8937

17874

26812

35749

44686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3070

6140

9210

12280

15350

<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:

0.408

AC:

61961

AN:

151996

Hom.:

12846

Cov.:

AF XY:

0.406

AC XY:

30202

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.377

AC:

15592

AN:

41412

American (AMR)

AF:

0.448

AC:

6841

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.498

AC:

1728

AN:

3472

East Asian (EAS)

AF:

0.212

AC:

1092

AN:

5162

South Asian (SAS)

AF:

0.464

AC:

2235

AN:

4820

European-Finnish (FIN)

AF:

0.388

AC:

4100

AN:

10564

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.426

AC:

28947

AN:

67962

Other (OTH)

AF:

0.421

AC:

889

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1875

3750

5625

7500

9375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.423

Hom.:

24963

Bravo

AF:

0.411

Asia WGS

AF:

0.332

AC:

1155

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.6

(source)

DANN

Benign

0.84

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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