NM_152641.4:c.638-1336A>G

Variant names:

• chr12-45820084-A-G
• rs11183212
• NM_152641.4:c.638-1336A>G

Variant summary

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

The NM_152641.4(ARID2):​c.638-1336A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 151,922 control chromosomes in the GnomAD database, including 2,082 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 0.15 (2082 hom., cov: 31)
• Consequence: ARID2 NM_152641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 10 publications found

Genes affected

ARID2 (HGNC:18037): (AT-rich interaction domain 2) This gene encodes a member of the AT-rich interactive domain (ARID)-containing family of DNA-binding proteins. Members of the ARID family have roles in embryonic patterning, cell lineage gene regulation, cell cycle control, transcriptional regulation and chromatin structure modification. This protein functions as a subunit of the polybromo- and BRG1-associated factor or PBAF (SWI/SNF-B) chromatin remodeling complex which facilitates ligand-dependent transcriptional activation by nuclear receptors. Mutations in this gene are associated with hepatocellular carcinomas. A pseudogene of this gene is found on chromosome1. [provided by RefSeq, Dec 2016]

ARID2 Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Orphanet, ClinGen
• Coffin-Siris syndrome 6

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID2	NM_152641.4	c.638-1336A>G		intron_variant	Intron 5 of 20	ENST00000334344.11	NP_689854.2
ARID2	NM_001347839.2	c.638-1336A>G		intron_variant	Intron 5 of 19		NP_001334768.1
ARID2	XM_047428489.1	c.638-1336A>G		intron_variant	Intron 5 of 16		XP_047284445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID2	ENST00000334344.11	c.638-1336A>G		intron_variant	Intron 5 of 20	1	NM_152641.4	ENSP00000335044.6
ARID2	ENST00000422737.7	c.638-1336A>G		intron_variant	Intron 5 of 19	1		ENSP00000415650.3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22109 AN: 151808 Hom.: 2079 Cov.: 31

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.146 AC: 22110 AN: 151922 Hom.: 2082 Cov.: 31 AF XY: 0.146 AC XY: 10838 AN XY: 74236

African (AFR) AF: 0.0343 AC: 1420 AN: 41450

American (AMR) AF: 0.113 AC: 1726 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3470

East Asian (EAS) AF: 0.142 AC: 731 AN: 5162

South Asian (SAS) AF: 0.180 AC: 867 AN: 4808

European-Finnish (FIN) AF: 0.196 AC: 2068 AN: 10536

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14103 AN: 67932

Other (OTH) AF: 0.160 AC: 337 AN: 2106

Alfa AF: 0.191 Hom.: 1697

Bravo AF: 0.134

Asia WGS AF: 0.148 AC: 516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.0050
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: rs11183212; hg19: chr12-46213867;