1-26696463-G-A

Variant names:

• chr1-26696463-G-A
• rs2124739963
• NM_006015.6:c.60G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_006015.6(ARID1A):​c.60G>A​(p.Pro20Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000176 in 1,133,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: ARID1A NM_006015.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.30
• Publications: 0 publications found

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]

ARID1A Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• intellectual disability, autosomal dominant 14

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae)

LOC124900417 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 1-26696463-G-A is Benign according to our data. Variant chr1-26696463-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2887907.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.3 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1A	NM_006015.6	c.60G>A	p.Pro20Pro	synonymous_variant	Exon 1 of 20	ENST00000324856.13	NP_006006.3
ARID1A	NM_139135.4	c.60G>A	p.Pro20Pro	synonymous_variant	Exon 1 of 20		NP_624361.1
LOC124900417	XM_047439473.1	c.-58C>T		upstream_gene_variant			XP_047295429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1A	ENST00000324856.13	c.60G>A	p.Pro20Pro	synonymous_variant	Exon 1 of 20	1	NM_006015.6	ENSP00000320485.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000176 AC: 2 AN: 1133996 Hom.: 0 Cov.: 35 AF XY: 0.00000364 AC XY: 2 AN XY: 549752

African (AFR) AF: 0.0000435 AC: 1 AN: 23012

American (AMR) AF: 0.00 AC: 0 AN: 10830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15454

East Asian (EAS) AF: 0.0000387 AC: 1 AN: 25830

South Asian (SAS) AF: 0.00 AC: 0 AN: 36508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3042

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 950732

Other (OTH) AF: 0.00 AC: 0 AN: 44986

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.97
PhyloP100		2.3
PromoterAI		0.050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.0
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs2124739963; hg19: chr1-27022954;