1-153746270-G-A

Position:

• chr1-153746270-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_023015.5(INTS3):​c.319-687G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,924 control chromosomes in the GnomAD database, including 18,863 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 0.48 (18863 hom., cov: 31)
• Consequence: INTS3 NM_023015.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INTS3	NM_023015.5	c.319-687G>A		intron_variant		ENST00000318967.7	NP_075391.3
INTS3	NM_001324475.2	c.319-687G>A		intron_variant			NP_001311404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS3	ENST00000318967.7	c.319-687G>A		intron_variant		1	NM_023015.5	ENSP00000318641.2
INTS3	ENST00000435409.6	c.319-687G>A		intron_variant		2		ENSP00000404290.2
INTS3	ENST00000481797.5	n.471-687G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73551 AN: 151806 Hom.: 18826 Cov.: 31

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.485 AC: 73637 AN: 151924 Hom.: 18863 Cov.: 31 AF XY: 0.483 AC XY: 35835 AN XY: 74266

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.462

Alfa AF: 0.428 Hom.: 14793

Bravo AF: 0.480

Asia WGS AF: 0.520 AC: 1808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Benign	0.73

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: rs9426902; hg19: chr1-153718746;