rs241202

Positions:

• chr8-28776168-C-G
• chr8-28776168-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018250.4(INTS9):​c.1396-242G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 412,902 control chromosomes in the GnomAD database, including 53,417 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 0.50 (19632 hom., cov: 32)
  • Exomes 𝑓: 0.50 (33785 hom.)
• Consequence: INTS9 NM_018250.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.30

Genes affected

INTS9 (HGNC:25592): (integrator complex subunit 9) This gene encodes a subunit of the Integrator complex. This protein complex binds the C-terminal domain of RNA polymerase II and likely plays a role in small nuclear RNA processing. The encoded protein has similarities to the subunits of the cleavage and polyadenylation specificity factor complex. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS9	NM_018250.4	c.1396-242G>C		intron_variant		ENST00000521022.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS9	ENST00000521022.6	c.1396-242G>C		intron_variant		1	NM_018250.4	P1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76504 AN: 151932 Hom.: 19623 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.500 AC: 130459 AN: 260852 Hom.: 33785 Cov.: 2 AF XY: 0.500 AC XY: 66931 AN XY: 133764

Gnomad4 AFR exome AF: 0.517

Gnomad4 AMR exome AF: 0.477

Gnomad4 ASJ exome AF: 0.516

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.408

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.543

Gnomad4 OTH exome AF: 0.507

GnomAD4 genome AF: 0.503 AC: 76551 AN: 152050 Hom.: 19632 Cov.: 32 AF XY: 0.500 AC XY: 37167 AN XY: 74340

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.510

Alfa AF: 0.398 Hom.: 1130

Bravo AF: 0.506

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0020
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs241202; hg19: chr8-28633685;