8-19834515-A-C

Position:

• chr8-19834515-A-C

Variant summary

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

The NM_018142.4(INTS10):​c.1530+1194A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,968 control chromosomes in the GnomAD database, including 19,172 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 0.50 (19172 hom., cov: 32)
• Consequence: INTS10 NM_018142.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS10	NM_018142.4	c.1530+1194A>C		intron_variant		ENST00000397977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS10	ENST00000397977.8	c.1530+1194A>C		intron_variant		2	NM_018142.4	P1
INTS10	ENST00000518799.1	c.277+1194A>C		intron_variant		5
INTS10	ENST00000521357.5	c.*376+1194A>C		intron_variant, NMD_transcript_variant		5
INTS10	ENST00000519493.1	n.163+1194A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75860 AN: 151850 Hom.: 19145 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.500 AC: 75935 AN: 151968 Hom.: 19172 Cov.: 32 AF XY: 0.503 AC XY: 37365 AN XY: 74268

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.518

Alfa AF: 0.357 Hom.: 1086

Bravo AF: 0.502

Asia WGS AF: 0.497 AC: 1732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.016
DANN	Benign	0.28

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: rs2934; hg19: chr8-19692026;