rs17018310

Positions:

• chr1-211980901-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-1.0).
• 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INTS7	NM_015434.4	c.1230+192G>A		intron_variant		ENST00000366994.8	NP_056249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS7	ENST00000366994.8	c.1230+192G>A		intron_variant		1	NM_015434.4	ENSP00000355961	P1

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

Gnomad4 AFR AF: 0.0461

Gnomad4 AMR AF: 0.0203

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0218

Gnomad4 NFE AF: 0.0208

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0237 Hom.: 14

Bravo AF: 0.0262

Asia WGS AF: 0.0200 AC: 71 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	0.26
DANN	Benign	0.64

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: rs17018310; hg19: chr1-212154243; COSMIC: COSV65344016; COSMIC: COSV65344016;