rs7310702

Variant names:

• chr12-45855017-T-C
• rs7310702
• NM_152641.4:c.4773+2121T>C

Variant summary

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

The NM_152641.4(ARID2):​c.4773+2121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,202 control chromosomes in the GnomAD database, including 3,062 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 0.11 (3062 hom., cov: 32)
• Consequence: ARID2 NM_152641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID2	NM_152641.4	c.4773+2121T>C		intron_variant	Intron 15 of 20	ENST00000334344.11	NP_689854.2
ARID2	NM_001347839.2	c.4773+2121T>C		intron_variant	Intron 15 of 19		NP_001334768.1
ARID2	XM_047428489.1	c.4831+780T>C		intron_variant	Intron 16 of 16		XP_047284445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID2	ENST00000334344.11	c.4773+2121T>C		intron_variant	Intron 15 of 20	1	NM_152641.4	ENSP00000335044.6

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16963 AN: 152082 Hom.: 3051 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0451

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00384

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00126

Gnomad OTH AF: 0.0712

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

GnomAD4 genome AF: 0.112 AC: 17010 AN: 152202 Hom.: 3062 Cov.: 32 AF XY: 0.109 AC XY: 8121 AN XY: 74434

African (AFR) AF: 0.377 AC: 15625 AN: 41460

American (AMR) AF: 0.0451 AC: 689 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.00385 AC: 20 AN: 5190

South Asian (SAS) AF: 0.0852 AC: 411 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00126 AC: 86 AN: 68022

Other (OTH) AF: 0.0714 AC: 151 AN: 2114

Alfa AF: 0.102 Hom.: 333

Bravo AF: 0.124

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.49
PhyloP100		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs7310702; hg19: chr12-46248800;