1-26695829-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The XM_047439473.1(LOC124900417):c.326C>T(p.Ala109Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000686 in 985,236 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (1 hom.)
• Consequence: LOC124900417 XM_047439473.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.90

Genes affected

LOC124900417 (HGNC:):

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-26695829-G-A is Benign according to our data. Variant chr1-26695829-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1211712.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124900417	XM_047439473.1	c.326C>T	p.Ala109Val	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1A	ENST00000430799.7	c.-13+2212G>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.00382 AC: 581 AN: 152014 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00814

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0424

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.00192

GnomAD4 exome AF: 0.000114 AC: 95 AN: 833110 Hom.: 1 Cov.: 30 AF XY: 0.0000780 AC XY: 30 AN XY: 384714

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000970

Gnomad4 EAS exome AF: 0.00909

Gnomad4 SAS exome AF: 0.000486

Gnomad4 FIN exome AF: 0.0254

Gnomad4 NFE exome AF: 0.0000407

Gnomad4 OTH exome AF: 0.000403

GnomAD4 genome AF: 0.00382 AC: 581 AN: 152126 Hom.: 12 Cov.: 32 AF XY: 0.00539 AC XY: 401 AN XY: 74358

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00816

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0424

Gnomad4 NFE AF: 0.00113

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00302 Hom.: 0

Bravo AF: 0.000631

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 04, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	15
Dann	Benign	0.95

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs573303670; hg19: chr1-27022320;