Genetic Variant NM_018142.4:c.442-501T>C (chr8-19821938-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_018142.4(INTS10):c.442-501T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,556 control chromosomes in the GnomAD database, including 13,288 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 ( 13270 hom., cov: 32)

Exomes 𝑓: 0.25 ( 18 hom. )

Consequence

INTS10
NM_018142.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.57

Publications

4 publications found

Variant links:

Genes affected

INTS10 (HGNC:25548): (integrator complex subunit 10) INTS10 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]

INTS10 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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018142.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
INTS10	NM_018142.4	MANE Select	c.442-501T>C	intron	N/A	NP_060612.2	Q9NVR2
INTS10	NM_001353505.2		c.442-501T>C	intron	N/A	NP_001340434.1
INTS10	NM_001353506.2		c.442-501T>C	intron	N/A	NP_001340435.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
INTS10	ENST00000397977.8	TSL:2 MANE Select	c.442-501T>C	intron	N/A	ENSP00000381064.3	Q9NVR2
INTS10	ENST00000884209.1		c.442-501T>C	intron	N/A	ENSP00000554268.1
INTS10	ENST00000884210.1		c.442-501T>C	intron	N/A	ENSP00000554269.1

Frequencies

GnomAD3 genomes

AF:

0.407

AC:

61902

AN:

151908

Hom.:

13253

Cov.:

show subpopulations

Gnomad AFR

AF:

0.518

Gnomad AMI

AF:

0.484

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.479

Gnomad EAS

AF:

0.302

Gnomad SAS

AF:

0.444

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.405

GnomAD4 exome

AF:

0.247

AC:

131

AN:

530

Hom.:

Cov.:

AF XY:

0.230

AC XY:

AN XY:

326

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.458

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.213

AC:

AN:

390

Other (OTH)

AF:

0.375

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

61971

AN:

152026

Hom.:

13270

Cov.:

AF XY:

0.411

AC XY:

30526

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.519

AC:

21503

AN:

41448

American (AMR)

AF:

0.458

AC:

6991

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.479

AC:

1662

AN:

3470

East Asian (EAS)

AF:

0.301

AC:

1556

AN:

5162

South Asian (SAS)

AF:

0.445

AC:

2141

AN:

4808

European-Finnish (FIN)

AF:

0.338

AC:

3580

AN:

10582

Middle Eastern (MID)

AF:

0.517

AC:

151

AN:

292

European-Non Finnish (NFE)

AF:

0.340

AC:

23101

AN:

67976

Other (OTH)

AF:

0.401

AC:

846

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1836

3672

5508

7344

9180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<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:

0.366

Hom.:

5281

Bravo

AF:

0.420

Asia WGS

AF:

0.405

AC:

1411

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.52

(source)

DANN

Benign

0.61

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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