rs7812549

chr8-19849658-A-G

Variant summary

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

The NM_018142.4(INTS10):c.1977-1991A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,146 control chromosomes in the GnomAD database, including 2,041 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 0.16 (2041 hom., cov: 32)
• Consequence: INTS10 NM_018142.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

Genes affected

INTS10 (HGNC:25548): (integrator complex subunit 10) INTS10 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS10	NM_018142.4	c.1977-1991A>G		intron_variant		ENST00000397977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS10	ENST00000397977.8	c.1977-1991A>G		intron_variant		2	NM_018142.4	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23974 AN: 152028 Hom.: 2043 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.158 AC: 23977 AN: 152146 Hom.: 2041 Cov.: 32 AF XY: 0.160 AC XY: 11924 AN XY: 74378

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.162

Alfa AF: 0.154 Hom.: 918

Bravo AF: 0.164

Asia WGS AF: 0.185 AC: 643 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.6
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7812549; hg19: chr8-19707169;