rs2251235

Variant names:

• chr7-1494152-A-C
• rs2251235
• NM_001080453.3:c.1911-241T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080453.3(INTS1):​c.1911-241T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,118 control chromosomes in the GnomAD database, including 23,826 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 0.54 (23826 hom., cov: 33)
• Consequence: INTS1 NM_001080453.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 4 publications found

Genes affected

INTS1 (HGNC:24555): (integrator complex subunit 1) INTS1 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]

INTS1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS1	NM_001080453.3	c.1911-241T>G		intron_variant	Intron 14 of 47	ENST00000404767.8	NP_001073922.2
INTS1	XM_011515260.2	c.1911-241T>G		intron_variant	Intron 14 of 47		XP_011513562.1
INTS1	XM_011515262.3	c.1911-241T>G		intron_variant	Intron 14 of 27		XP_011513564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS1	ENST00000404767.8	c.1911-241T>G		intron_variant	Intron 14 of 47	5	NM_001080453.3	ENSP00000385722.3

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81747 AN: 152000 Hom.: 23791 Cov.: 33

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.538 AC: 81832 AN: 152118 Hom.: 23826 Cov.: 33 AF XY: 0.540 AC XY: 40148 AN XY: 74342

African (AFR) AF: 0.770 AC: 31986 AN: 41522

American (AMR) AF: 0.449 AC: 6870 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1383 AN: 3470

East Asian (EAS) AF: 0.699 AC: 3614 AN: 5172

South Asian (SAS) AF: 0.520 AC: 2509 AN: 4822

European-Finnish (FIN) AF: 0.490 AC: 5179 AN: 10574

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28500 AN: 67954

Other (OTH) AF: 0.518 AC: 1091 AN: 2108

Alfa AF: 0.491 Hom.: 2571

Bravo AF: 0.544

Asia WGS AF: 0.611 AC: 2126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.58
PhyloP100		-0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2251235; hg19: chr7-1533788;