rs11933466

Positions:

• chr4-105891575-G-A

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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS12	ENST00000510876.1	c.-163+4204C>T		intron_variant		4		ENSP00000422856

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;