chr11-77990987-T-A

Variant names:

• chr11-77990987-T-A
• rs2276441
• NM_033547.4:c.246+121A>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+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
• Publications: 4 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=-0.9).
• 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 rank	MANE	Protein	UniProt
INTS4	NM_033547.4	c.246+121A>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+121A>T		intron_variant	Intron 2 of 22	1	NM_033547.4	ENSP00000434466.1

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

African (AFR) AF: 0.851 AC: 13766 AN: 16176

American (AMR) AF: 0.691 AC: 15764 AN: 22802

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 11371 AN: 15316

East Asian (EAS) AF: 0.768 AC: 25615 AN: 33334

South Asian (SAS) AF: 0.534 AC: 27869 AN: 52214

European-Finnish (FIN) AF: 0.775 AC: 30716 AN: 39614

Middle Eastern (MID) AF: 0.607 AC: 1821 AN: 3002

European-Non Finnish (NFE) AF: 0.703 AC: 303928 AN: 432054

Other (OTH) AF: 0.698 AC: 22840 AN: 32738

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

African (AFR) AF: 0.845 AC: 35044 AN: 41486

American (AMR) AF: 0.703 AC: 10749 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2571 AN: 3468

East Asian (EAS) AF: 0.725 AC: 3756 AN: 5180

South Asian (SAS) AF: 0.528 AC: 2542 AN: 4814

European-Finnish (FIN) AF: 0.797 AC: 8429 AN: 10576

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47676 AN: 67986

Other (OTH) AF: 0.725 AC: 1528 AN: 2108

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
PhyloP100		-0.50
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: rs2276441; hg19: chr11-77702033;