11-77960095-T-G

Variant names:

• chr11-77960095-T-G
• rs2034499
• NM_033547.4:c.708+246A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_033547.4(INTS4):​c.708+246A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 152,044 control chromosomes in the GnomAD database, including 56 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 0.015 (56 hom., cov: 30)
• Consequence: INTS4 NM_033547.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• 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=-0.94).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0151 (2297/152044) while in subpopulation AFR AF = 0.0509 (2112/41496). AF 95% confidence interval is 0.0491. There are 56 homozygotes in GnomAd4. There are 1086 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 56 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS4	NM_033547.4	c.708+246A>C		intron_variant	Intron 6 of 22	ENST00000534064.6	NP_291025.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS4	ENST00000534064.6	c.708+246A>C		intron_variant	Intron 6 of 22	1	NM_033547.4	ENSP00000434466.1

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2299 AN: 151926 Hom.: 56 Cov.: 30

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00940

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0130

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

GnomAD4 genome AF: 0.0151 AC: 2297 AN: 152044 Hom.: 56 Cov.: 30 AF XY: 0.0146 AC XY: 1086 AN XY: 74322

African (AFR) AF: 0.0509 AC: 2112 AN: 41496

American (AMR) AF: 0.00938 AC: 143 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67972

Other (OTH) AF: 0.0129 AC: 27 AN: 2100

Alfa AF: 0.00 Hom.: 2846

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.17
DANN	Benign	0.37
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism

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: rs2034499; hg19: chr11-77671141;