rs2279351

chr12-26937617-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018164.3(INTS13):c.-12+179T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,260 control chromosomes in the GnomAD database, including 1,618 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 0.14 (1618 hom., cov: 32)
  • Exomes 𝑓: 0.18 (0 hom.)
• Consequence: INTS13 NM_018164.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

Genes affected

INTS13 (HGNC:20174): (integrator complex subunit 13) Involved in regulation of mitotic cell cycle. Acts upstream of or within centrosome localization; mitotic spindle organization; and protein localization to nuclear envelope. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS13	NM_018164.3	c.-12+179T>G		intron_variant		ENST00000261191.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS13	ENST00000261191.12	c.-12+179T>G		intron_variant		1	NM_018164.3	P1
INTS13	ENST00000537336.1	c.-12+651T>G		intron_variant		3
INTS13	ENST00000538727.5	c.-4+179T>G		intron_variant		4
INTS13	ENST00000544548.5	c.-12+41T>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20942 AN: 152098 Hom.: 1611 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0474

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.182 AC: 8 AN: 44 Hom.: 0 Cov.: 0 AF XY: 0.206 AC XY: 7 AN XY: 34

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.200

GnomAD4 genome AF: 0.138 AC: 20966 AN: 152216 Hom.: 1618 Cov.: 32 AF XY: 0.139 AC XY: 10352 AN XY: 74420

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0475

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.149

Alfa AF: 0.138 Hom.: 3095

Bravo AF: 0.143

Asia WGS AF: 0.103 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	14
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2279351; hg19: chr12-27090550;