chr11-77990815-T-A

Variant names:

• chr11-77990815-T-A
• rs3819256
• NM_033547.4:c.246+293A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

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 = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS4	NM_033547.4	c.246+293A>T		intron_variant	Intron 2 of 22	ENST00000534064.6	NP_291025.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS4	ENST00000534064.6	c.246+293A>T		intron_variant	Intron 2 of 22	1	NM_033547.4	ENSP00000434466.1

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

African (AFR) AF: 0.575 AC: 23827 AN: 41414

American (AMR) AF: 0.528 AC: 8067 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1548 AN: 3470

East Asian (EAS) AF: 0.590 AC: 3051 AN: 5172

South Asian (SAS) AF: 0.346 AC: 1663 AN: 4812

European-Finnish (FIN) AF: 0.597 AC: 6294 AN: 10536

Middle Eastern (MID) AF: 0.390 AC: 113 AN: 290

European-Non Finnish (NFE) AF: 0.491 AC: 33410 AN: 67976

Other (OTH) AF: 0.523 AC: 1102 AN: 2106

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
PhyloP100		0.33
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: rs3819256; hg19: chr11-77701861;