rs17018310

Variant names:

• chr1-211980901-C-T
• rs17018310
• NM_015434.4:c.1230+192G>A

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.1230+192G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 152,152 control chromosomes in the GnomAD database, including 58 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 (58 hom., cov: 32)
• Consequence: INTS7 NM_015434.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 2 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=-1.0).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0261 (3978/152152) while in subpopulation AFR AF = 0.0461 (1912/41506). AF 95% confidence interval is 0.0443. There are 58 homozygotes in GnomAd4. There are 1865 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 58 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS7	NM_015434.4	MANE Select	c.1230+192G>A		intron	N/A	NP_056249.1
	INTS7	NM_001199811.2		c.1230+192G>A		intron	N/A	NP_001186740.1
	INTS7	NM_001199812.2		c.1230+192G>A		intron	N/A	NP_001186741.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS7	ENST00000366994.8	TSL:1 MANE Select	c.1230+192G>A		intron	N/A	ENSP00000355961.3
	INTS7	ENST00000366993.7	TSL:1	c.1230+192G>A		intron	N/A	ENSP00000355960.3
	INTS7	ENST00000469606.5	TSL:1	n.*1000+192G>A		intron	N/A	ENSP00000481687.1

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 3970 AN: 152034 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0461

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0203

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.00311

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: 0.0261 AC: 3978 AN: 152152 Hom.: 58 Cov.: 32 AF XY: 0.0251 AC XY: 1865 AN XY: 74394

African (AFR) AF: 0.0461 AC: 1912 AN: 41506

American (AMR) AF: 0.0203 AC: 310 AN: 15262

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

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

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4822

European-Finnish (FIN) AF: 0.0218 AC: 231 AN: 10590

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

European-Non Finnish (NFE) AF: 0.0208 AC: 1411 AN: 68000

Other (OTH) AF: 0.0194 AC: 41 AN: 2112

Alfa AF: 0.0236 Hom.: 22

Bravo AF: 0.0262

Asia WGS AF: 0.0200 AC: 71 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	0.26
DANN	Benign	0.64
PhyloP100		-1.2
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: rs17018310; hg19: chr1-212154243; COSMIC: COSV65344016; COSMIC: COSV65344016;