dbSNP rs4345834: 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:

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=-0.7).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS3	NM_023015.5 link	c.2552+108G>A		intron_variant	Intron 25 of 29	ENST00000318967.7	NP_075391.3	Q68E01-2
INTS3	NM_001324475.2 link	c.2552+108G>A		intron_variant	Intron 26 of 30		NP_001311404.1	Q68E01-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS3	ENST00000318967.7 link	c.2552+108G>A		intron_variant	Intron 25 of 29	1	NM_023015.5	ENSP00000318641.2		Q68E01-2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over