rs10516529

Variant names:

• chr4-105878159-T-G
• rs10516529
• ENST00000510876.1:c.-163+17620A>C

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS12	ENST00000510876.1	c.-163+17620A>C		intron_variant	Intron 1 of 3	4		ENSP00000422856.1

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;