11-77973577-A-G

Variant names:

• chr11-77973577-A-G
• rs11237340
• NM_033547.4:c.471+5419T>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 5 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 = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS4	NM_033547.4	c.471+5419T>C		intron_variant	Intron 4 of 22	ENST00000534064.6	NP_291025.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS4	ENST00000534064.6	c.471+5419T>C		intron_variant	Intron 4 of 22	1	NM_033547.4	ENSP00000434466.1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113296 AN: 151732 Hom.: 42855 Cov.: 29

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

African (AFR) AF: 0.859 AC: 35606 AN: 41438

American (AMR) AF: 0.705 AC: 10744 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2568 AN: 3468

East Asian (EAS) AF: 0.729 AC: 3759 AN: 5158

South Asian (SAS) AF: 0.527 AC: 2533 AN: 4802

European-Finnish (FIN) AF: 0.798 AC: 8393 AN: 10518

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47640 AN: 67902

Other (OTH) AF: 0.727 AC: 1535 AN: 2110

Alfa AF: 0.718 Hom.: 20878

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
PhyloP100		-2.4
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: rs11237340; hg19: chr11-77684623;