8-19821938-T-C

Position:

• chr8-19821938-T-C

Variant summary

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

The NM_018142.4(INTS10):​c.442-501T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,556 control chromosomes in the GnomAD database, including 13,288 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 0.41 (13270 hom., cov: 32)
  • Exomes 𝑓: 0.25 (18 hom.)
• Consequence: INTS10 NM_018142.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS10	NM_018142.4	c.442-501T>C		intron_variant		ENST00000397977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS10	ENST00000397977.8	c.442-501T>C		intron_variant		2	NM_018142.4	P1
INTS10	ENST00000522081.1	n.990T>C		non_coding_transcript_exon_variant	1/3	2
INTS10	ENST00000523869.1	c.*131-501T>C		intron_variant, NMD_transcript_variant		5
INTS10	ENST00000521758.5	n.390-501T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61902 AN: 151908 Hom.: 13253 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.247 AC: 131 AN: 530 Hom.: 18 Cov.: 0 AF XY: 0.230 AC XY: 75 AN XY: 326

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.458

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.408 AC: 61971 AN: 152026 Hom.: 13270 Cov.: 32 AF XY: 0.411 AC XY: 30526 AN XY: 74314

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.401

Alfa AF: 0.366 Hom.: 4676

Bravo AF: 0.420

Asia WGS AF: 0.405 AC: 1411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.52
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs7005767; hg19: chr8-19679449;