chr1-1312114-T-A

Variant names:

• chr1-1312114-T-A
• rs12103
• NM_017871.6:c.1641A>T

Variant summary

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

The NM_017871.6(INTS11):​c.1641A>T​(p.Pro547Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,425,594 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.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: INTS11 NM_017871.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75
• Publications: 61 publications found

Genes affected

INTS11 (HGNC:26052): (integrator complex subunit 11) The Integrator complex contains at least 12 subunits and associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates the 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690). INTS11, or CPSF3L, is the catalytic subunit of the Integrator complex (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

INTS11 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities

  Inheritance: AR Classification: MODERATE Submitted by: G2P

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=-0.95).
• BP7: Synonymous conserved (PhyloP=-2.75 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017871.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS11	NM_017871.6	MANE Select	c.1641A>T	p.Pro547Pro	synonymous	Exon 16 of 17	NP_060341.2
	INTS11	NM_001256456.2		c.1659A>T	p.Pro553Pro	synonymous	Exon 18 of 19	NP_001243385.1
	INTS11	NM_001256460.2		c.1554A>T	p.Pro518Pro	synonymous	Exon 17 of 18	NP_001243389.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS11	ENST00000435064.6	TSL:1 MANE Select	c.1641A>T	p.Pro547Pro	synonymous	Exon 16 of 17	ENSP00000413493.2
	INTS11	ENST00000323275.10	TSL:1	n.2029A>T		non_coding_transcript_exon	Exon 15 of 16
	INTS11	ENST00000462432.5	TSL:1	n.2444A>T		non_coding_transcript_exon	Exon 12 of 13

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.00 AC: 0 AN: 202050 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1425594 Hom.: 0 Cov.: 54 AF XY: 0.00000284 AC XY: 2 AN XY: 704734

African (AFR) AF: 0.00 AC: 0 AN: 32856

American (AMR) AF: 0.00 AC: 0 AN: 40558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25282

East Asian (EAS) AF: 0.00 AC: 0 AN: 38086

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5344

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092892

Other (OTH) AF: 0.00 AC: 0 AN: 58848

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0060
DANN	Benign	0.58
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12103; hg19: chr1-1247494;