rs10516529

chr4-105878159-T-G

Variant summary

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

The ENST00000510876.1(INTS12):c.-163+17620A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,234 control chromosomes in the GnomAD database, including 1,502 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 0.11 (1502 hom., cov: 32)
• Consequence: INTS12 ENST00000510876.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356

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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS12	ENST00000510876.1	c.-163+17620A>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17147 AN: 152116 Hom.: 1488 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0905

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.0255

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.113 AC: 17196 AN: 152234 Hom.: 1502 Cov.: 32 AF XY: 0.107 AC XY: 7967 AN XY: 74436

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.0903

Gnomad4 ASJ AF: 0.0700

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0215

Gnomad4 FIN AF: 0.0255

Gnomad4 NFE AF: 0.0674

Gnomad4 OTH AF: 0.124

Alfa AF: 0.0851 Hom.: 233

Bravo AF: 0.125

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	14
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: rs10516529; hg19: chr4-106799316;