Variant chr11-77903546-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_033547.4(INTS4):c.2091G>A(p.Ala697=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

INTS4
NM_033547.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.403

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:

AAMDC (HGNC:30205): (adipogenesis associated Mth938 domain containing) Predicted to be involved in positive regulation of fat cell differentiation. Predicted to act upstream of or within negative regulation of apoptotic process and positive regulation of transcription by RNA polymerase II. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

AAMDC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 11-77903546-C-T is Benign according to our data. Variant chr11-77903546-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642195.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.403 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS4	NM_033547.4 linkuse as main transcript	c.2091G>A	p.Ala697=	synonymous_variant	17/23	ENST00000534064.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS4	ENST00000534064.6 linkuse as main transcript	c.2091G>A	p.Ala697=	synonymous_variant	17/23	1	NM_033547.4	P3	Q96HW7-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

174

AN:

141322

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00342

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000300

Gnomad EAS

AF:

0.000631

Gnomad SAS

AF:

0.00116

Gnomad FIN

AF:

0.000534

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000217

Gnomad OTH

AF:

0.00101

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000357

AC:

AN:

1456844

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

724804

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.0000909

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000541

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00123

AC:

174

AN:

141424

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

69270

show subpopulations

Gnomad4 AFR

AF:

0.00341

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.000300

Gnomad4 EAS

AF:

0.000632

Gnomad4 SAS

AF:

0.00116

Gnomad4 FIN

AF:

0.000534

Gnomad4 NFE

AF:

0.000217

Gnomad4 OTH

AF:

0.000998

Alfa

AF:

0.00331

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

INTS4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

9.9

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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