NM_020395.4:c.-9-472A>G

Variant names:

• chr4-105700486-T-C
• rs7659526
• NM_020395.4:c.-9-472A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020395.4(INTS12):​c.-9-472A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 151,766 control chromosomes in the GnomAD database, including 5,948 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 0.24 (5948 hom., cov: 31)
• Consequence: INTS12 NM_020395.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 3 publications found

Genes affected

INTS12 (HGNC:25067): (integrator complex subunit 12) INTS12 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

ARHGEF38 (HGNC:25968): (Rho guanine nucleotide exchange factor 38) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ARHGEF38 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

LOC124900748 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020395.4. 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
	INTS12	NM_020395.4	MANE Select	c.-9-472A>G		intron	N/A	NP_065128.2
	INTS12	NM_001142471.2		c.-9-472A>G		intron	N/A	NP_001135943.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS12	ENST00000340139.10	TSL:1 MANE Select	c.-9-472A>G		intron	N/A	ENSP00000340737.5
	INTS12	ENST00000451321.6	TSL:1	c.-9-472A>G		intron	N/A	ENSP00000415433.2
	INTS12	ENST00000394735.5	TSL:5	c.-9-472A>G		intron	N/A	ENSP00000378221.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35713 AN: 151648 Hom.: 5924 Cov.: 31

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.0683

Gnomad SAS AF: 0.0856

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.236 AC: 35782 AN: 151766 Hom.: 5948 Cov.: 31 AF XY: 0.229 AC XY: 16973 AN XY: 74200

African (AFR) AF: 0.475 AC: 19627 AN: 41304

American (AMR) AF: 0.229 AC: 3497 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 792 AN: 3464

East Asian (EAS) AF: 0.0683 AC: 353 AN: 5172

South Asian (SAS) AF: 0.0854 AC: 411 AN: 4810

European-Finnish (FIN) AF: 0.0597 AC: 630 AN: 10550

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9703 AN: 67916

Other (OTH) AF: 0.255 AC: 537 AN: 2104

Alfa AF: 0.189 Hom.: 4595

Bravo AF: 0.263

Asia WGS AF: 0.111 AC: 385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.5
DANN	Benign	0.45
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7659526; hg19: chr4-106621643;