12-45729823-C-G

Variant summary

Our verdict is Benign. Variant got -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 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.45

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID2	NM_152641.4	c.-14C>G		5_prime_UTR_variant	1/21	ENST00000334344.11
ARID2	NM_001347839.2	c.-14C>G		5_prime_UTR_variant	1/20
ARID2	XM_047428489.1	c.-14C>G		5_prime_UTR_variant	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID2	ENST00000334344.11	c.-14C>G		5_prime_UTR_variant	1/21	1	NM_152641.4	P1
ARID2	ENST00000422737.7	c.-14C>G		5_prime_UTR_variant	1/20	1
ARID2	ENST00000700074.1	n.118C>G		non_coding_transcript_exon_variant	1/4
ARID2	ENST00000427628.5			upstream_gene_variant		5

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

GnomAD3 exomes AF: 0.00872 AC: 1977 AN: 226770 Hom.: 80 AF XY: 0.0117 AC XY: 1453 AN XY: 124250

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 SAS exome AF: 0.0675

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

Gnomad4 AFR exome AF: 0.0000601

Gnomad4 AMR exome AF: 0.000115

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.0670

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000840

Gnomad4 OTH exome AF: 0.00408

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

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0674

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00238

Alfa AF: 0.000940 Hom.: 0

Bravo AF: 0.000480

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	18
Dann	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs375590924; hg19: chr12-46123606;