rs2276441

Positions:

• chr11-77990987-T-A
• chr11-77990987-T-C
• chr11-77990987-T-G

Variant summary

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

The NM_033547.4(INTS4):​c.246+121A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 799,354 control chromosomes in the GnomAD database, including 203,058 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 0.74 (42380 hom., cov: 32)
  • Exomes 𝑓: 0.70 (160678 hom.)
• Consequence: INTS4 NM_033547.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496

Genes affected

INTS4 (HGNC:25048): (integrator complex subunit 4) INTS4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS4	NM_033547.4	c.246+121A>T		intron_variant		ENST00000534064.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS4	ENST00000534064.6	c.246+121A>T		intron_variant		1	NM_033547.4	P3

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112771 AN: 151986 Hom.: 42347 Cov.: 32

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.725

GnomAD4 exome AF: 0.701 AC: 453690 AN: 647250 Hom.: 160678 AF XY: 0.693 AC XY: 232322 AN XY: 335188

Gnomad4 AFR exome AF: 0.851

Gnomad4 AMR exome AF: 0.691

Gnomad4 ASJ exome AF: 0.742

Gnomad4 EAS exome AF: 0.768

Gnomad4 SAS exome AF: 0.534

Gnomad4 FIN exome AF: 0.775

Gnomad4 NFE exome AF: 0.703

Gnomad4 OTH exome AF: 0.698

GnomAD4 genome AF: 0.742 AC: 112861 AN: 152104 Hom.: 42380 Cov.: 32 AF XY: 0.741 AC XY: 55092 AN XY: 74354

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.725

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.797

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.725

Alfa AF: 0.714 Hom.: 4818

Bravo AF: 0.747

Asia WGS AF: 0.615 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.77

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: rs2276441; hg19: chr11-77702033;