rs17018311

Variant names:

• chr1-211981666-T-C
• rs17018311
• NM_015434.4:c.1133-476A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015434.4(INTS7):​c.1133-476A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 152,258 control chromosomes in the GnomAD database, including 57 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 0.026 (57 hom., cov: 32)
• Consequence: INTS7 NM_015434.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 13 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=-0.57).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0258 (3932/152258) while in subpopulation AFR AF = 0.045 (1871/41550). AF 95% confidence interval is 0.0433. There are 57 homozygotes in GnomAd4. There are 1837 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 57 AR gene

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.1133-476A>G		intron	N/A	NP_056249.1	Q9NVH2-1
	INTS7	NM_001199811.2		c.1133-476A>G		intron	N/A	NP_001186740.1	Q9NVH2-2
	INTS7	NM_001199812.2		c.1133-476A>G		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.1133-476A>G		intron	N/A	ENSP00000355961.3	Q9NVH2-1
	INTS7	ENST00000366993.7	TSL:1	c.1133-476A>G		intron	N/A	ENSP00000355960.3	Q9NVH2-2
	INTS7	ENST00000469606.5	TSL:1	n.*903-476A>G		intron	N/A	ENSP00000481687.1	A0A087WYC2

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3924 AN: 152140 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0451

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0201

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0258 AC: 3932 AN: 152258 Hom.: 57 Cov.: 32 AF XY: 0.0247 AC XY: 1837 AN XY: 74456

African (AFR) AF: 0.0450 AC: 1871 AN: 41550

American (AMR) AF: 0.0201 AC: 307 AN: 15288

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

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4828

European-Finnish (FIN) AF: 0.0218 AC: 231 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0207 AC: 1409 AN: 68008

Other (OTH) AF: 0.0194 AC: 41 AN: 2110

Alfa AF: 0.0214 Hom.: 114

Bravo AF: 0.0259

Asia WGS AF: 0.0210 AC: 71 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.91
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

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: rs17018311; hg19: chr1-212155008;