NM_020395.4:c.-171-297C>A

Variant names:

• chr4-105704106-G-T
• rs10516523
• NM_020395.4:c.-171-297C>A

Variant summary

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

The NM_020395.4(INTS12):​c.-171-297C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,218 control chromosomes in the GnomAD database, including 16,830 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 0.39 (16830 hom., cov: 31)
• Consequence: INTS12 NM_020395.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690
• Publications: 7 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 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.-171-297C>A		intron	N/A	NP_065128.2
	INTS12	NM_001142471.2		c.-9-4092C>A		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.-171-297C>A		intron	N/A	ENSP00000340737.5
	INTS12	ENST00000451321.6	TSL:1	c.-9-4092C>A		intron	N/A	ENSP00000415433.2
	INTS12	ENST00000394735.5	TSL:5	c.-10+1584C>A		intron	N/A	ENSP00000378221.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58747 AN: 151102 Hom.: 16773 Cov.: 31

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.389 AC: 58850 AN: 151218 Hom.: 16830 Cov.: 31 AF XY: 0.379 AC XY: 27959 AN XY: 73728

African (AFR) AF: 0.808 AC: 33402 AN: 41346

American (AMR) AF: 0.344 AC: 5231 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1137 AN: 3462

East Asian (EAS) AF: 0.103 AC: 525 AN: 5116

South Asian (SAS) AF: 0.161 AC: 770 AN: 4792

European-Finnish (FIN) AF: 0.122 AC: 1248 AN: 10196

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15274 AN: 67800

Other (OTH) AF: 0.401 AC: 844 AN: 2106

Alfa AF: 0.290 Hom.: 21481

Bravo AF: 0.426

Asia WGS AF: 0.179 AC: 622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.0
DANN	Benign	0.65
PhyloP100		0.069
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: rs10516523; hg19: chr4-106625263;