rs3819256

chr11-77990815-T-Achr11-77990815-T-Cchr11-77990815-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+293A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,950 control chromosomes in the GnomAD database, including 20,946 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 0.52 (20946 hom., cov: 31)
• Consequence: INTS4 NM_033547.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS4	NM_033547.4	c.246+293A>T		intron_variant		ENST00000534064.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS4	ENST00000534064.6	c.246+293A>T		intron_variant		1	NM_033547.4	P3

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79300 AN: 151832 Hom.: 20921 Cov.: 31

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.522 AC: 79381 AN: 151950 Hom.: 20946 Cov.: 31 AF XY: 0.524 AC XY: 38905 AN XY: 74252

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.523

Alfa AF: 0.496 Hom.: 2359

Bravo AF: 0.529

Asia WGS AF: 0.464 AC: 1613 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	3.4
Dann	Benign	0.76

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: rs3819256; hg19: chr11-77701861;