rs12041194

Variant names:

• chr1-153741776-G-A
• rs12041194
• NM_023015.5:c.318+408G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
INTS3	NM_023015.5	c.318+408G>A		intron_variant	Intron 3 of 29	ENST00000318967.7	NP_075391.3
INTS3	NM_001324475.2	c.318+408G>A		intron_variant	Intron 4 of 30		NP_001311404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS3	ENST00000318967.7	c.318+408G>A		intron_variant	Intron 3 of 29	1	NM_023015.5	ENSP00000318641.2
INTS3	ENST00000435409.6	c.318+408G>A		intron_variant	Intron 4 of 30	2		ENSP00000404290.2
INTS3	ENST00000481797.5	n.470+408G>A		intron_variant	Intron 3 of 28	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

African (AFR) AF: 0.215 AC: 8927 AN: 41494

American (AMR) AF: 0.245 AC: 3745 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1190 AN: 3466

East Asian (EAS) AF: 0.536 AC: 2766 AN: 5164

South Asian (SAS) AF: 0.418 AC: 2018 AN: 4828

European-Finnish (FIN) AF: 0.436 AC: 4605 AN: 10564

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26857 AN: 67982

Other (OTH) AF: 0.332 AC: 702 AN: 2112

Alfa AF: 0.366 Hom.: 17380

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
PhyloP100		1.1
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: rs12041194; hg19: chr1-153714252;