1-211975070-G-T

Variant names:

• chr1-211975070-G-T
• rs41502452
• NM_015434.4:c.1815+96C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015434.4(INTS7):​c.1815+96C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 787,348 control chromosomes in the GnomAD database, including 206 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)
  • Exomes 𝑓: 0.018 (149 hom.)
• Consequence: INTS7 NM_015434.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832

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=-0.89).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0258 (3930/152252) while in subpopulation AFR AF= 0.0451 (1875/41544). AF 95% confidence interval is 0.0434. There are 57 homozygotes in gnomad4. There are 1836 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS7	NM_015434.4	c.1815+96C>A		intron_variant	Intron 13 of 19	ENST00000366994.8	NP_056249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS7	ENST00000366994.8	c.1815+96C>A		intron_variant	Intron 13 of 19	1	NM_015434.4	ENSP00000355961.3

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3922 AN: 152134 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0201

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0216

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.0183 AC: 11602 AN: 635096 Hom.: 149 AF XY: 0.0175 AC XY: 5840 AN XY: 334548

Gnomad4 AFR exome AF: 0.0425

Gnomad4 AMR exome AF: 0.0112

Gnomad4 ASJ exome AF: 0.0160

Gnomad4 EAS exome AF: 0.000478

Gnomad4 SAS exome AF: 0.00362

Gnomad4 FIN exome AF: 0.0213

Gnomad4 NFE exome AF: 0.0211

Gnomad4 OTH exome AF: 0.0197

GnomAD4 genome AF: 0.0258 AC: 3930 AN: 152252 Hom.: 57 Cov.: 32 AF XY: 0.0247 AC XY: 1836 AN XY: 74454

Gnomad4 AFR AF: 0.0451

Gnomad4 AMR AF: 0.0201

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0216

Gnomad4 NFE AF: 0.0207

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0132 Hom.: 7

Bravo AF: 0.0259

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	-0.89
CADD	Benign	1.3
DANN	Benign	0.66

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: rs41502452; hg19: chr1-212148412;