rs7110670

Positions:

• chr11-77986205-G-A
• chr11-77986205-G-C

Variant summary

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

The NM_033547.4(INTS4):​c.247-4629C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,126 control chromosomes in the GnomAD database, including 42,501 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 (42501 hom., cov: 32)
• Consequence: INTS4 NM_033547.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464

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 = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INTS4	NM_033547.4	c.247-4629C>T		intron_variant		ENST00000534064.6	NP_291025.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS4	ENST00000534064.6	c.247-4629C>T		intron_variant		1	NM_033547.4	ENSP00000434466	P3

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112912 AN: 152008 Hom.: 42457 Cov.: 32

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.743 AC: 113016 AN: 152126 Hom.: 42501 Cov.: 32 AF XY: 0.742 AC XY: 55185 AN XY: 74386

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.797

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.727

Alfa AF: 0.693 Hom.: 5983

Bravo AF: 0.748

Asia WGS AF: 0.615 AC: 2141 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	1.3
DANN	Benign	0.55

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: rs7110670; hg19: chr11-77697251;