12-45729823-C-G

Variant names:

• chr12-45729823-C-G
• rs375590924
• NM_152641.4:c.-14C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152641.4(ARID2):​c.-14C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,601,770 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (12 hom., cov: 30)
  • Exomes 𝑓: 0.0042 (281 hom.)
• Consequence: ARID2 NM_152641.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.45
• Publications: 0 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: Orphanet, Illumina, ClinGen
• Coffin-Siris syndrome 6

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 12-45729823-C-G is Benign according to our data. Variant chr12-45729823-C-G is described in ClinVar as Benign. ClinVar VariationId is 1246175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152641.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID2	NM_152641.4	MANE Select	c.-14C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	NP_689854.2
	ARID2	NM_152641.4	MANE Select	c.-14C>G		5_prime_UTR	Exon 1 of 21	NP_689854.2
	ARID2	NM_001347839.2		c.-14C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	NP_001334768.1	F8WCU9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID2	ENST00000334344.11	TSL:1 MANE Select	c.-14C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	ENSP00000335044.6	Q68CP9-1
	ARID2	ENST00000422737.7	TSL:1	c.-14C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	ENSP00000415650.3	F8WCU9
	ARID2	ENST00000334344.11	TSL:1 MANE Select	c.-14C>G		5_prime_UTR	Exon 1 of 21	ENSP00000335044.6	Q68CP9-1

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 345 AN: 152000 Hom.: 12 Cov.: 30

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0678

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00872 AC: 1977 AN: 226770 AF XY: 0.0117

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000234

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000149

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00416 AC: 6025 AN: 1449654 Hom.: 281 Cov.: 31 AF XY: 0.00599 AC XY: 4312 AN XY: 720138

African (AFR) AF: 0.0000601 AC: 2 AN: 33266

American (AMR) AF: 0.000115 AC: 5 AN: 43428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25846

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39290

South Asian (SAS) AF: 0.0670 AC: 5664 AN: 84570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51182

Middle Eastern (MID) AF: 0.00216 AC: 12 AN: 5558

European-Non Finnish (NFE) AF: 0.0000840 AC: 93 AN: 1106642

Other (OTH) AF: 0.00408 AC: 244 AN: 59872

GnomAD4 genome AF: 0.00226 AC: 344 AN: 152116 Hom.: 12 Cov.: 30 AF XY: 0.00340 AC XY: 253 AN XY: 74362

African (AFR) AF: 0.0000963 AC: 4 AN: 41520

American (AMR) AF: 0.000262 AC: 4 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.0674 AC: 325 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67958

Other (OTH) AF: 0.00238 AC: 5 AN: 2102

Alfa AF: 0.000940 Hom.: 0

Bravo AF: 0.000480

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.87
PhyloP100		1.5
PromoterAI		-0.036	Neutral
Mutation Taster		=300/0	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: rs375590924; hg19: chr12-46123606;