rs12041194

Positions:

• chr1-153741776-G-A
• chr1-153741776-G-C

Variant summary

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

The NM_023015.5(INTS3):​c.318+408G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,086 control chromosomes in the GnomAD database, including 9,447 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 0.34 (9447 hom., cov: 32)
• Consequence: INTS3 NM_023015.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

Genes affected

INTS3 (HGNC:26153): (integrator complex subunit 3) The protein encoded by this gene can form a complex with human single-strand DNA binding proteins 1 or 2 (hSSB1 and hSSB2) and other proteins to mediate genome stability and the DNA damage response. The encoded protein is also part of a multiprotein complex that interacts with the C-terminal domain of RNA polymerase II large subunit to help regulate processing of U1 and U2 small nuclear RNAs. [provided by RefSeq, May 2016]

INTS3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INTS3	NM_023015.5	c.318+408G>A		intron_variant		ENST00000318967.7	NP_075391.3
INTS3	NM_001324475.2	c.318+408G>A		intron_variant			NP_001311404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS3	ENST00000318967.7	c.318+408G>A		intron_variant		1	NM_023015.5	ENSP00000318641.2
INTS3	ENST00000435409.6	c.318+408G>A		intron_variant		2		ENSP00000404290.2
INTS3	ENST00000481797.5	n.470+408G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51245 AN: 151968 Hom.: 9455 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.337 AC: 51237 AN: 152086 Hom.: 9447 Cov.: 32 AF XY: 0.338 AC XY: 25144 AN XY: 74336

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.332

Alfa AF: 0.373 Hom.: 14103

Bravo AF: 0.317

Asia WGS AF: 0.443 AC: 1543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.0
DANN	Benign	0.41

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: rs12041194; hg19: chr1-153714252;