1-26747433-C-T

Position:

• chr1-26747433-C-T

Variant summary

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

The NM_006015.6(ARID1A):​c.1921-13423C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 152,262 control chromosomes in the GnomAD database, including 330 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 0.060 (330 hom., cov: 32)
• Consequence: ARID1A NM_006015.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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=-0.64).
• 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.1921-13423C>T		intron_variant		ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.1921-13423C>T		intron_variant			NP_624361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.1921-13423C>T		intron_variant		1	NM_006015.6	ENSP00000320485

Frequencies

GnomAD3 genomes AF: 0.0596 AC: 9066 AN: 152144 Hom.: 329 Cov.: 32

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0550

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0835

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0798

Gnomad OTH AF: 0.0549

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

GnomAD4 genome AF: 0.0596 AC: 9071 AN: 152262 Hom.: 330 Cov.: 32 AF XY: 0.0591 AC XY: 4400 AN XY: 74450

Gnomad4 AFR AF: 0.0295

Gnomad4 AMR AF: 0.0549

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.0195

Gnomad4 SAS AF: 0.0489

Gnomad4 FIN AF: 0.0835

Gnomad4 NFE AF: 0.0798

Gnomad4 OTH AF: 0.0548

Alfa AF: 0.0414 Hom.: 37

Bravo AF: 0.0557

Asia WGS AF: 0.0400 AC: 137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.77

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: rs12752833; hg19: chr1-27073924;