rs7938133

Variant names:

• chr11-77987478-C-T
• rs7938133
• ENST00000527522.1:c.*176G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000527522.1(INTS4):​c.*176G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 301,484 control chromosomes in the GnomAD database, including 72,759 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 0.74 (42467 hom., cov: 32)
  • Exomes 𝑓: 0.63 (30292 hom.)
• Consequence: INTS4 ENST00000527522.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.27
• Publications: 15 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.84 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000527522.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS4	NM_033547.4	MANE Select	c.246+3630G>A		intron	N/A	NP_291025.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS4	ENST00000527522.1	TSL:1	c.*176G>A		3_prime_UTR	Exon 3 of 3	ENSP00000435758.1	E9PIM3
	INTS4	ENST00000534064.6	TSL:1 MANE Select	c.246+3630G>A		intron	N/A	ENSP00000434466.1	Q96HW7-1
	INTS4	ENST00000529807.5	TSL:1	c.246+3630G>A		intron	N/A	ENSP00000433644.1	Q96HW7-2

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112855 AN: 151992 Hom.: 42423 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.724

GnomAD4 exome AF: 0.630 AC: 94044 AN: 149374 Hom.: 30292 Cov.: 0 AF XY: 0.611 AC XY: 50960 AN XY: 83378

African (AFR) AF: 0.830 AC: 2237 AN: 2696

American (AMR) AF: 0.629 AC: 4310 AN: 6852

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2328 AN: 3358

East Asian (EAS) AF: 0.677 AC: 2955 AN: 4362

South Asian (SAS) AF: 0.496 AC: 17230 AN: 34740

European-Finnish (FIN) AF: 0.735 AC: 5181 AN: 7046

Middle Eastern (MID) AF: 0.572 AC: 1198 AN: 2094

European-Non Finnish (NFE) AF: 0.665 AC: 54020 AN: 81206

Other (OTH) AF: 0.653 AC: 4585 AN: 7020

GnomAD4 genome AF: 0.743 AC: 112959 AN: 152110 Hom.: 42467 Cov.: 32 AF XY: 0.742 AC XY: 55145 AN XY: 74350

African (AFR) AF: 0.847 AC: 35163 AN: 41508

American (AMR) AF: 0.703 AC: 10746 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2571 AN: 3472

East Asian (EAS) AF: 0.729 AC: 3775 AN: 5180

South Asian (SAS) AF: 0.528 AC: 2546 AN: 4822

European-Finnish (FIN) AF: 0.797 AC: 8400 AN: 10546

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47664 AN: 67982

Other (OTH) AF: 0.724 AC: 1528 AN: 2110

Alfa AF: 0.701 Hom.: 19240

Bravo AF: 0.747

Asia WGS AF: 0.617 AC: 2146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.018
DANN	Benign	0.33
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7938133; hg19: chr11-77698524;