1-26696721-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006015.6(ARID1A):c.318C>T(p.Asn106=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,370,886 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (7 hom.)
• Consequence: ARID1A NM_006015.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0430

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-26696721-C-T is Benign according to our data. Variant chr1-26696721-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 434315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.043 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00184 (278/150892) while in subpopulation NFE AF= 0.0032 (216/67558). AF 95% confidence interval is 0.00285. There are 0 homozygotes in gnomad4. There are 113 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 278 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1A	NM_006015.6	c.318C>T	p.Asn106=	synonymous_variant	1/20	ENST00000324856.13
ARID1A	NM_139135.4	c.318C>T	p.Asn106=	synonymous_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1A	ENST00000324856.13	c.318C>T	p.Asn106=	synonymous_variant	1/20	1	NM_006015.6
ARID1A	ENST00000457599.6	c.318C>T	p.Asn106=	synonymous_variant	1/20	5
ARID1A	ENST00000430799.7	c.-13+3104C>T		intron_variant		5		A2
ARID1A	ENST00000637465.1	c.-13+621C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00184 AC: 278 AN: 150784 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000487

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00132

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000289

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00320

Gnomad OTH AF: 0.000965

GnomAD3 exomes AF: 0.00144 AC: 42 AN: 29208 Hom.: 0 AF XY: 0.00135 AC XY: 24 AN XY: 17780

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00759

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000377

Gnomad NFE exome AF: 0.00199

Gnomad OTH exome AF: 0.00134

GnomAD4 exome AF: 0.00304 AC: 3709 AN: 1219994 Hom.: 7 Cov.: 35 AF XY: 0.00301 AC XY: 1800 AN XY: 597530

Gnomad4 AFR exome AF: 0.000208

Gnomad4 AMR exome AF: 0.00146

Gnomad4 ASJ exome AF: 0.00715

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000558

Gnomad4 FIN exome AF: 0.000602

Gnomad4 NFE exome AF: 0.00343

Gnomad4 OTH exome AF: 0.00231

GnomAD4 genome AF: 0.00184 AC: 278 AN: 150892 Hom.: 0 Cov.: 32 AF XY: 0.00153 AC XY: 113 AN XY: 73738

Gnomad4 AFR AF: 0.000486

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000289

Gnomad4 NFE AF: 0.00320

Gnomad4 OTH AF: 0.000954

Alfa AF: 0.00254 Hom.: 0

Bravo AF: 0.00208

Asia WGS AF: 0.00118 AC: 4 AN: 3416

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	ARID1A: BP4, BP7, BS1 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 27, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 11, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 21, 2020

- -

Intellectual disability, autosomal dominant 14 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	13
Dann	Benign	0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs551186176; hg19: chr1-27023212; COSMIC: COSV104411797; COSMIC: COSV104411797;