1-1312114-T-C

Position:

• chr1-1312114-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017871.6(INTS11):​c.1641A>G​(p.Pro547=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,568,016 control chromosomes in the GnomAD database, including 435,138 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 0.59 (30166 hom., cov: 25)
  • Exomes 𝑓: 0.73 (404972 hom.)
• Consequence: INTS11 NM_017871.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP7: Synonymous conserved (PhyloP=-2.75 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INTS11	NM_017871.6	c.1641A>G	p.Pro547=	synonymous_variant	16/17	ENST00000435064.6	NP_060341.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS11	ENST00000435064.6	c.1641A>G	p.Pro547=	synonymous_variant	16/17	1	NM_017871.6	ENSP00000413493	P1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 84374 AN: 143416 Hom.: 30177 Cov.: 25

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.0182

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.795

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.609

GnomAD3 exomes AF: 0.558 AC: 112752 AN: 202050 Hom.: 39716 AF XY: 0.571 AC XY: 61883 AN XY: 108306

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.330

Gnomad ASJ exome AF: 0.821

Gnomad EAS exome AF: 0.0136

Gnomad SAS exome AF: 0.381

Gnomad FIN exome AF: 0.718

Gnomad NFE exome AF: 0.797

Gnomad OTH exome AF: 0.655

GnomAD4 exome AF: 0.728 AC: 1036800 AN: 1424504 Hom.: 404972 Cov.: 54 AF XY: 0.722 AC XY: 508066 AN XY: 704086

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.356

Gnomad4 ASJ exome AF: 0.821

Gnomad4 EAS exome AF: 0.0114

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.732

Gnomad4 NFE exome AF: 0.809

Gnomad4 OTH exome AF: 0.671

GnomAD4 genome AF: 0.588 AC: 84346 AN: 143512 Hom.: 30166 Cov.: 25 AF XY: 0.575 AC XY: 40105 AN XY: 69736

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.0181

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.817

Gnomad4 OTH AF: 0.600

Alfa AF: 0.732 Hom.: 13103

Bravo AF: 0.531

Asia WGS AF: 0.169 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0060
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs12103; hg19: chr1-1247494; COSMIC: COSV60088100; COSMIC: COSV60088100;