rs11727189

Variant names:

• chr4-105697983-G-T
• rs11727189
• NM_020395.4:c.156+1867C>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.156+1867C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 152,258 control chromosomes in the GnomAD database, including 250 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 0.054 (250 hom., cov: 32)
• Consequence: INTS12 NM_020395.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 26 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.066 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS12	NM_020395.4	c.156+1867C>A		intron_variant	Intron 3 of 7	ENST00000340139.10	NP_065128.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS12	ENST00000340139.10	c.156+1867C>A		intron_variant	Intron 3 of 7	1	NM_020395.4	ENSP00000340737.5

Frequencies

GnomAD3 genomes AF: 0.0536 AC: 8156 AN: 152140 Hom.: 251 Cov.: 32

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0697

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.0762

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

GnomAD4 genome AF: 0.0536 AC: 8154 AN: 152258 Hom.: 250 Cov.: 32 AF XY: 0.0511 AC XY: 3802 AN XY: 74440

African (AFR) AF: 0.0407 AC: 1691 AN: 41554

American (AMR) AF: 0.0694 AC: 1062 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 283 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.0209 AC: 101 AN: 4826

European-Finnish (FIN) AF: 0.0316 AC: 335 AN: 10616

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0641 AC: 4358 AN: 68012

Other (OTH) AF: 0.0759 AC: 160 AN: 2108

Alfa AF: 0.0168 Hom.: 26

Bravo AF: 0.0564

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11727189; hg19: chr4-106619140;