rs17331332

Positions:

• chr4-105886950-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+8829C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 152,088 control chromosomes in the GnomAD database, including 208 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 0.045 (208 hom., cov: 31)
• Consequence: INTS12 ENST00000510876.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0649 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+8829C>T		intron_variant		4		ENSP00000422856

Frequencies

GnomAD3 genomes AF: 0.0453 AC: 6887 AN: 151970 Hom.: 209 Cov.: 31

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0665

Gnomad OTH AF: 0.0675

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

GnomAD4 genome AF: 0.0452 AC: 6880 AN: 152088 Hom.: 208 Cov.: 31 AF XY: 0.0425 AC XY: 3162 AN XY: 74350

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.0619

Gnomad4 ASJ AF: 0.0701

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0209

Gnomad4 FIN AF: 0.0253

Gnomad4 NFE AF: 0.0665

Gnomad4 OTH AF: 0.0672

Alfa AF: 0.0506 Hom.: 44

Bravo AF: 0.0474

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.52
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17331332; hg19: chr4-106808107;