8-19849658-A-G

Variant names:

• chr8-19849658-A-G
• rs7812549
• NM_018142.4:c.1977-1991A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018142.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS10	NM_018142.4	MANE Select	c.1977-1991A>G		intron	N/A	NP_060612.2
	INTS10	NM_001353505.2		c.2057+419A>G		intron	N/A	NP_001340434.1
	INTS10	NM_001353506.2		c.2054+419A>G		intron	N/A	NP_001340435.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS10	ENST00000397977.8	TSL:2 MANE Select	c.1977-1991A>G		intron	N/A	ENSP00000381064.3
	INTS10	ENST00000520827.1	TSL:3	n.*88-1991A>G		intron	N/A	ENSP00000428671.1
	INTS10	ENST00000523772.1	TSL:5	c.362+419A>G		intron	N/A	ENSP00000428608.1

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

African (AFR) AF: 0.134 AC: 5558 AN: 41498

American (AMR) AF: 0.226 AC: 3455 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3468

East Asian (EAS) AF: 0.305 AC: 1576 AN: 5166

South Asian (SAS) AF: 0.153 AC: 737 AN: 4822

European-Finnish (FIN) AF: 0.139 AC: 1474 AN: 10608

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9927 AN: 67986

Other (OTH) AF: 0.162 AC: 342 AN: 2114

Alfa AF: 0.155 Hom.: 1036

Bravo AF: 0.164

Asia WGS AF: 0.185 AC: 643 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.63
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7812549; hg19: chr8-19707169;