Variant 8-94824884-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_017864.4(INTS8):c.131-9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,562,226 control chromosomes in the GnomAD database, including 307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.016 ( 38 hom., cov: 30)

Exomes 𝑓: 0.014 ( 269 hom. )

Consequence

INTS8
NM_017864.4 intron

Scores

Splicing: ADA: 0.00004624

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0800

Variant links:

Genes affected

INTS8 (HGNC:26048): (integrator complex subunit 8) This gene encodes a subunit of the Integrator complex which is involved in the cleavage of small nuclear RNAs U1 and U2 within the nucleus. The encoded protein associates with RNA polymerase II and is recruited to the U1 and U2 small nuclear RNA genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

INTS8 links:

INTS8 (HGNC:):

INTS8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 8-94824884-A-G is Benign according to our data. Variant chr8-94824884-A-G is described in ClinVar as [Benign]. Clinvar id is 3055544.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr8-94824884-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
INTS8	NM_017864.4 linkuse as main transcript	c.131-9A>G	intron_variant	ENST00000523731.6	NP_060334.2	Q75QN2-1
INTS8	XM_047421951.1 linkuse as main transcript	c.131-9A>G	intron_variant		XP_047277907.1
INTS8	NR_073444.2 linkuse as main transcript	n.276-9A>G	intron_variant
INTS8	NR_073445.2 linkuse as main transcript	n.276-9A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS8	ENST00000523731.6 linkuse as main transcript	c.131-9A>G		intron_variant		1	NM_017864.4	ENSP00000430338.1		Q75QN2-1

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2342

AN:

144928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0175

Gnomad ASJ

AF:

0.0569

Gnomad EAS

AF:

0.0754

Gnomad SAS

AF:

0.0214

Gnomad FIN

AF:

0.0211

Gnomad MID

AF:

0.0252

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.0200

GnomAD3 exomes

AF:

0.0191

AC:

4477

AN:

234464

Hom.:

107

AF XY:

0.0193

AC XY:

2466

AN XY:

127568

show subpopulations

Gnomad AFR exome

AF:

0.00985

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.0535

Gnomad EAS exome

AF:

0.0767

Gnomad SAS exome

AF:

0.0174

Gnomad FIN exome

AF:

0.0134

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.0201

GnomAD4 exome

AF:

0.0138

AC:

19588

AN:

1417184

Hom.:

269

Cov.:

AF XY:

0.0140

AC XY:

9907

AN XY:

705732

show subpopulations

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.0130

Gnomad4 ASJ exome

AF:

0.0524

Gnomad4 EAS exome

AF:

0.0699

Gnomad4 SAS exome

AF:

0.0166

Gnomad4 FIN exome

AF:

0.0143

Gnomad4 NFE exome

AF:

0.0104

Gnomad4 OTH exome

AF:

0.0194

GnomAD4 genome

AF:

0.0162

AC:

2354

AN:

145042

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1196

AN XY:

69950

show subpopulations

Gnomad4 AFR

AF:

0.0126

Gnomad4 AMR

AF:

0.0175

Gnomad4 ASJ

AF:

0.0569

Gnomad4 EAS

AF:

0.0754

Gnomad4 SAS

AF:

0.0214

Gnomad4 FIN

AF:

0.0211

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.0198

Alfa

AF:

0.0142

Hom.:

Bravo

AF:

0.0156

Asia WGS

AF:

0.0410

AC:

142

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

INTS8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.0

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000046

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over