rs11264342

Variant names:

• chr1-153738792-T-C
• rs11264342
• NM_023015.5:c.151-1859T>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.151-1859T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,100 control chromosomes in the GnomAD database, including 13,905 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 (13905 hom., cov: 32)
• Consequence: INTS3 NM_023015.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS3	NM_023015.5	c.151-1859T>C		intron_variant	Intron 1 of 29	ENST00000318967.7	NP_075391.3
INTS3	NM_001324475.2	c.151-1859T>C		intron_variant	Intron 2 of 30		NP_001311404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS3	ENST00000318967.7	c.151-1859T>C		intron_variant	Intron 1 of 29	1	NM_023015.5	ENSP00000318641.2
INTS3	ENST00000435409.6	c.151-1859T>C		intron_variant	Intron 2 of 30	2		ENSP00000404290.2
INTS3	ENST00000481797.5	n.303-1859T>C		intron_variant	Intron 1 of 28	2

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63104 AN: 151982 Hom.: 13911 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.415 AC: 63113 AN: 152100 Hom.: 13905 Cov.: 32 AF XY: 0.418 AC XY: 31095 AN XY: 74352

African (AFR) AF: 0.278 AC: 11531 AN: 41510

American (AMR) AF: 0.395 AC: 6028 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1491 AN: 3466

East Asian (EAS) AF: 0.669 AC: 3468 AN: 5186

South Asian (SAS) AF: 0.466 AC: 2250 AN: 4828

European-Finnish (FIN) AF: 0.520 AC: 5490 AN: 10556

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31433 AN: 67974

Other (OTH) AF: 0.422 AC: 893 AN: 2114

Alfa AF: 0.424 Hom.: 2245

Bravo AF: 0.400

Asia WGS AF: 0.528 AC: 1837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.6
DANN	Benign	0.57
PhyloP100		-0.44
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: rs11264342; hg19: chr1-153711268;