rs11933466

Variant names:

• chr4-105891575-G-A
• rs11933466
• ENST00000510876.1:c.-163+4204C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000510876.1(INTS12):​c.-163+4204C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,890 control chromosomes in the GnomAD database, including 16,979 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 0.39 (16979 hom., cov: 32)
• Consequence: INTS12 ENST00000510876.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417

Genes affected

INTS12 (HGNC:25067): (integrator complex subunit 12) INTS12 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS12	ENST00000510876.1	c.-163+4204C>T		intron_variant	Intron 1 of 3	4		ENSP00000422856.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59479 AN: 151772 Hom.: 16923 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.0885

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.405

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.392 AC: 59584 AN: 151890 Hom.: 16979 Cov.: 32 AF XY: 0.382 AC XY: 28373 AN XY: 74228

Gnomad4 AFR AF: 0.805

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.0883

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.400

Alfa AF: 0.270 Hom.: 3290

Bravo AF: 0.429

Asia WGS AF: 0.212 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.6
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11933466; hg19: chr4-106812732;