dbSNP rs7938133: INTS4:c.*176G>A (chr11-77987478-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000527522.1(INTS4):c.*176G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 301,484 control chromosomes in the GnomAD database, including 72,759 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 0.74 ( 42467 hom., cov: 32)

Exomes 𝑓: 0.63 ( 30292 hom. )

Consequence

INTS4
ENST00000527522.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.27

Publications

15 publications found

Variant links:

Genes affected

INTS4 (HGNC:25048): (integrator complex subunit 4) INTS4 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]

INTS4 links:

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new If you want to explore the variant's impact on the transcript ENST00000527522.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-1.02).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000527522.1. 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
	INTS4	NM_033547.4	MANE Select	c.246+3630G>A		intron	N/A	NP_291025.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
INTS4	ENST00000527522.1	TSL:1	c.*176G>A	3_prime_UTR	Exon 3 of 3	ENSP00000435758.1	E9PIM3
INTS4	ENST00000534064.6	TSL:1 MANE Select	c.246+3630G>A	intron	N/A	ENSP00000434466.1	Q96HW7-1
INTS4	ENST00000529807.5	TSL:1	c.246+3630G>A	intron	N/A	ENSP00000433644.1	Q96HW7-2

Frequencies

GnomAD3 genomes

AF:

0.743

AC:

112855

AN:

151992

Hom.:

42423

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.703

Gnomad ASJ

AF:

0.740

Gnomad EAS

AF:

0.729

Gnomad SAS

AF:

0.526

Gnomad FIN

AF:

0.797

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.701

Gnomad OTH

AF:

0.724

GnomAD4 exome

AF:

0.630

AC:

94044

AN:

149374

Hom.:

30292

Cov.:

AF XY:

0.611

AC XY:

50960

AN XY:

83378

show subpopulations

African (AFR)

AF:

0.830

AC:

2237

AN:

2696

American (AMR)

AF:

0.629

AC:

4310

AN:

6852

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

2328

AN:

3358

East Asian (EAS)

AF:

0.677

AC:

2955

AN:

4362

South Asian (SAS)

AF:

0.496

AC:

17230

AN:

34740

European-Finnish (FIN)

AF:

0.735

AC:

5181

AN:

7046

Middle Eastern (MID)

AF:

0.572

AC:

1198

AN:

2094

European-Non Finnish (NFE)

AF:

0.665

AC:

54020

AN:

81206

Other (OTH)

AF:

0.653

AC:

4585

AN:

7020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

Heterozygous variant carriers

1257

2515

3772

5030

6287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.743

AC:

112959

AN:

152110

Hom.:

42467

Cov.:

AF XY:

0.742

AC XY:

55145

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.847

AC:

35163

AN:

41508

American (AMR)

AF:

0.703

AC:

10746

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.740

AC:

2571

AN:

3472

East Asian (EAS)

AF:

0.729

AC:

3775

AN:

5180

South Asian (SAS)

AF:

0.528

AC:

2546

AN:

4822

European-Finnish (FIN)

AF:

0.797

AC:

8400

AN:

10546

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.701

AC:

47664

AN:

67982

Other (OTH)

AF:

0.724

AC:

1528

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1471

2942

4413

5884

7355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<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:

0.701

Hom.:

19240

Bravo

AF:

0.747

Asia WGS

AF:

0.617

AC:

2146

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.018

(source)

DANN

Benign

0.33

PhyloP100

-3.3

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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