rs2124739865

Variant names:

• chr1-26696445-C-A
• rs2124739865
• NM_006015.6:c.42C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-26696445-C-A
• chr1-26696445-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006015.6(ARID1A):​c.42C>A​(p.Gly14Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G14G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID1A NM_006015.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• 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: ClinGen, Orphanet
• intellectual disability, autosomal dominant 14

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

LOC124900417 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=1.19 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006015.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1A	NM_006015.6	MANE Select	c.42C>A	p.Gly14Gly	synonymous	Exon 1 of 20	NP_006006.3
	ARID1A	NM_139135.4		c.42C>A	p.Gly14Gly	synonymous	Exon 1 of 20	NP_624361.1	O14497-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1A	ENST00000324856.13	TSL:1 MANE Select	c.42C>A	p.Gly14Gly	synonymous	Exon 1 of 20	ENSP00000320485.7	O14497-1
	ARID1A	ENST00000850904.1		c.42C>A	p.Gly14Gly	synonymous	Exon 1 of 20	ENSP00000520984.1	A0ABJ7H312
	ARID1A	ENST00000457599.7	TSL:5	c.42C>A	p.Gly14Gly	synonymous	Exon 1 of 20	ENSP00000387636.2	O14497-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1141944 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 554456

African (AFR) AF: 0.00 AC: 0 AN: 23202

American (AMR) AF: 0.00 AC: 0 AN: 11792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16024

East Asian (EAS) AF: 0.00 AC: 0 AN: 25888

South Asian (SAS) AF: 0.00 AC: 0 AN: 38882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3100

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 953718

Other (OTH) AF: 0.00 AC: 0 AN: 45358

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		1.2
PromoterAI		0.030	Neutral
Mutation Taster		=100/0	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: rs2124739865; hg19: chr1-27022936;