11-77973577-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033547.4(INTS4):​c.471+5419T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 151,850 control chromosomes in the GnomAD database, including 42,897 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 0.75 ( 42897 hom., cov: 29)

Consequence

INTS4
NM_033547.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.36
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
INTS4NM_033547.4 linkuse as main transcriptc.471+5419T>C intron_variant ENST00000534064.6 NP_291025.3 Q96HW7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
INTS4ENST00000534064.6 linkuse as main transcriptc.471+5419T>C intron_variant 1 NM_033547.4 ENSP00000434466.1 Q96HW7-1

Frequencies

GnomAD3 genomes
AF:
0.747
AC:
113296
AN:
151732
Hom.:
42855
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.859
Gnomad AMI
AF:
0.473
Gnomad AMR
AF:
0.705
Gnomad ASJ
AF:
0.740
Gnomad EAS
AF:
0.729
Gnomad SAS
AF:
0.526
Gnomad FIN
AF:
0.798
Gnomad MID
AF:
0.655
Gnomad NFE
AF:
0.702
Gnomad OTH
AF:
0.727
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.747
AC:
113398
AN:
151850
Hom.:
42897
Cov.:
29
AF XY:
0.746
AC XY:
55349
AN XY:
74202
show subpopulations
Gnomad4 AFR
AF:
0.859
Gnomad4 AMR
AF:
0.705
Gnomad4 ASJ
AF:
0.740
Gnomad4 EAS
AF:
0.729
Gnomad4 SAS
AF:
0.527
Gnomad4 FIN
AF:
0.798
Gnomad4 NFE
AF:
0.702
Gnomad4 OTH
AF:
0.727
Alfa
AF:
0.714
Hom.:
17566
Bravo
AF:
0.752
Asia WGS
AF:
0.616
AC:
2132
AN:
3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.45
DANN
Benign
0.43

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs11237340; hg19: chr11-77684623; API