NM_001080453.3:c.6372G>T

Variant names:

• chr7-1470931-C-A
• rs753542479
• NM_001080453.3:c.6372G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001080453.3(INTS1):​c.6372G>T​(p.Thr2124Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000702 in 1,424,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T2124T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: INTS1 NM_001080453.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.802
• Publications: 0 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, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=-0.802 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080453.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS1	NM_001080453.3	MANE Select	c.6372G>T	p.Thr2124Thr	synonymous	Exon 47 of 48	NP_001073922.2	Q8N201

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS1	ENST00000404767.8	TSL:5 MANE Select	c.6372G>T	p.Thr2124Thr	synonymous	Exon 47 of 48	ENSP00000385722.3	Q8N201
	INTS1	ENST00000951930.1		c.6615G>T	p.Thr2205Thr	synonymous	Exon 48 of 49	ENSP00000621989.1
	INTS1	ENST00000916004.1		c.6459G>T	p.Thr2153Thr	synonymous	Exon 47 of 48	ENSP00000586063.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000702 AC: 10 AN: 1424716 Hom.: 0 Cov.: 31 AF XY: 0.00000567 AC XY: 4 AN XY: 705466

African (AFR) AF: 0.0000308 AC: 1 AN: 32492

American (AMR) AF: 0.00 AC: 0 AN: 39108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25500

East Asian (EAS) AF: 0.00 AC: 0 AN: 37386

South Asian (SAS) AF: 0.00 AC: 0 AN: 81380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000822 AC: 9 AN: 1094390

Other (OTH) AF: 0.00 AC: 0 AN: 59120

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	2.7
DANN	Benign	0.52
PhyloP100		-0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs753542479; hg19: chr7-1510567;