rs12731749

Positions:

• chr1-26759071-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006015.6(ARID1A):​c.1921-1785T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 152,176 control chromosomes in the GnomAD database, including 320 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 0.057 (320 hom., cov: 32)
• Consequence: ARID1A NM_006015.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

Genes affected

ARID1A (HGNC:11110): (AT-rich interaction domain 1A) This gene encodes a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. It possesses at least two conserved domains that could be important for its function. First, it has a DNA-binding domain that can specifically bind an AT-rich DNA sequence known to be recognized by a SNF/SWI complex at the beta-globin locus. Second, the C-terminus of the protein can stimulate glucocorticoid receptor-dependent transcriptional activation. It is thought that the protein encoded by this gene confers specificity to the SNF/SWI complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.078 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.1921-1785T>C		intron_variant		ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.1921-1785T>C		intron_variant			NP_624361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.1921-1785T>C		intron_variant		1	NM_006015.6	ENSP00000320485

Frequencies

GnomAD3 genomes AF: 0.0568 AC: 8635 AN: 152058 Hom.: 319 Cov.: 32

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0538

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0798

Gnomad OTH AF: 0.0540

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

GnomAD4 genome AF: 0.0568 AC: 8641 AN: 152176 Hom.: 320 Cov.: 32 AF XY: 0.0565 AC XY: 4199 AN XY: 74382

Gnomad4 AFR AF: 0.0198

Gnomad4 AMR AF: 0.0537

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.0195

Gnomad4 SAS AF: 0.0484

Gnomad4 FIN AF: 0.0834

Gnomad4 NFE AF: 0.0798

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0644 Hom.: 48

Bravo AF: 0.0525

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12731749; hg19: chr1-27085562;