rs2358385

Variant names:

• chr1-211957092-C-T
• rs2358385
• NM_015434.4:c.2184-4391G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015434.4. 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
	INTS7	NM_015434.4	MANE Select	c.2184-4391G>A		intron	N/A	NP_056249.1	Q9NVH2-1
	INTS7	NM_001199811.2		c.2184-4391G>A		intron	N/A	NP_001186740.1	Q9NVH2-2
	INTS7	NM_001199812.2		c.2184-4391G>A		intron	N/A	NP_001186741.1	Q9NVH2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS7	ENST00000366994.8	TSL:1 MANE Select	c.2184-4391G>A		intron	N/A	ENSP00000355961.3	Q9NVH2-1
	INTS7	ENST00000366993.7	TSL:1	c.2184-4391G>A		intron	N/A	ENSP00000355960.3	Q9NVH2-2
	INTS7	ENST00000469606.5	TSL:1	n.*1954-4391G>A		intron	N/A	ENSP00000481687.1	A0A087WYC2

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

African (AFR) AF: 0.0825 AC: 3427 AN: 41544

American (AMR) AF: 0.0258 AC: 395 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4830

European-Finnish (FIN) AF: 0.0217 AC: 230 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0208 AC: 1417 AN: 68022

Other (OTH) AF: 0.0261 AC: 55 AN: 2110

Alfa AF: 0.0284 Hom.: 45

Bravo AF: 0.0388

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.078
DANN	Benign	0.19
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2358385; hg19: chr1-212130434;