rs7938648

chr11-77971836-A-Cchr11-77971836-A-Gchr11-77971836-A-T

Variant summary

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

The NM_033547.4(INTS4):c.471+7160T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 151,982 control chromosomes in the GnomAD database, including 44,263 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 0.76 (44263 hom., cov: 31)
• Consequence: INTS4 NM_033547.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.993

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS4	NM_033547.4	c.471+7160T>G		intron_variant		ENST00000534064.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS4	ENST00000534064.6	c.471+7160T>G		intron_variant		1	NM_033547.4	P3

Frequencies

GnomAD3 genomes AF: 0.757 AC: 114925 AN: 151864 Hom.: 44215 Cov.: 31

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.757 AC: 115035 AN: 151982 Hom.: 44263 Cov.: 31 AF XY: 0.755 AC XY: 56113 AN XY: 74280

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.710

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.739

Alfa AF: 0.614 Hom.: 1645

Bravo AF: 0.764

Asia WGS AF: 0.622 AC: 2166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.2
Dann	Benign	0.18

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: rs7938648; hg19: chr11-77682882;