rs2358385

Positions:

• chr1-211957092-C-T

Variant summary

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

The NM_015434.4(INTS7):​c.2184-4391G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 152,294 control chromosomes in the GnomAD database, including 156 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 0.037 (156 hom., cov: 32)
• Consequence: INTS7 NM_015434.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

Genes affected

INTS7 (HGNC:24484): (integrator complex subunit 7) This gene encodes a subunit of the integrator complex. The integrator complex associates with the C-terminal domain of RNA polymerase II and mediates 3'-end processing of the small nuclear RNAs U1 and U2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 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 (AFR) allele frequency at 95% confidence interval = 0.0802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS7	NM_015434.4	c.2184-4391G>A		intron_variant		ENST00000366994.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS7	ENST00000366994.8	c.2184-4391G>A		intron_variant		1	NM_015434.4	P1

Frequencies

GnomAD3 genomes AF: 0.0367 AC: 5586 AN: 152176 Hom.: 156 Cov.: 32

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0217

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.0244

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

GnomAD4 genome AF: 0.0368 AC: 5598 AN: 152294 Hom.: 156 Cov.: 32 AF XY: 0.0354 AC XY: 2634 AN XY: 74472

Gnomad4 AFR AF: 0.0825

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.0217

Gnomad4 NFE AF: 0.0208

Gnomad4 OTH AF: 0.0261

Alfa AF: 0.0280 Hom.: 31

Bravo AF: 0.0388

Asia WGS AF: 0.0210 AC: 73 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	0.078
DANN	Benign	0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs2358385; hg19: chr1-212130434;