dbSNP rs7005767: INTS10: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS10	NM_018142.4 link	c.442-501T>C		intron_variant	Intron 4 of 16	ENST00000397977.8	NP_060612.2	Q9NVR2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
INTS10	ENST00000397977.8 link	c.442-501T>C	intron_variant	Intron 4 of 16	2	NM_018142.4	ENSP00000381064.3	Q9NVR2
INTS10	ENST00000522081.1 link	n.990T>C	non_coding_transcript_exon_variant	Exon 1 of 3	2
INTS10	ENST00000521758.5 link	n.390-501T>C	intron_variant	Intron 3 of 3	2
INTS10	ENST00000523869.1 link	n.*131-501T>C	intron_variant	Intron 3 of 4	5		ENSP00000428107.1	H0YAU7

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over