rs1039830124

Variant names:

• chr1-26696484-C-T
• rs1039830124
• NM_006015.6:c.81C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-26696484-C-T
• chr1-26696484-C-A
• chr1-26696484-C-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_006015.6(ARID1A):​c.81C>T​(p.Ala27Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,249,372 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: ARID1A NM_006015.6 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.59
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 1-26696484-C-T is Benign according to our data. Variant chr1-26696484-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3030675.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.59 with no splicing effect.
• BS2: High AC in GnomAd4 at 5 AD gene.

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.81C>T	p.Ala27Ala	synonymous	Exon 1 of 20	NP_006006.3
	ARID1A	NM_139135.4		c.81C>T	p.Ala27Ala	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.81C>T	p.Ala27Ala	synonymous	Exon 1 of 20	ENSP00000320485.7	O14497-1
	ARID1A	ENST00000850904.1		c.81C>T	p.Ala27Ala	synonymous	Exon 1 of 20	ENSP00000520984.1	A0ABJ7H312
	ARID1A	ENST00000457599.7	TSL:5	c.81C>T	p.Ala27Ala	synonymous	Exon 1 of 20	ENSP00000387636.2	O14497-2

Frequencies

GnomAD3 genomes AF: 0.0000332 AC: 5 AN: 150798 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000592

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000364 AC: 40 AN: 1098574 Hom.: 0 Cov.: 35 AF XY: 0.0000304 AC XY: 16 AN XY: 526330

African (AFR) AF: 0.00 AC: 0 AN: 22528

American (AMR) AF: 0.00 AC: 0 AN: 8380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14148

East Asian (EAS) AF: 0.00 AC: 0 AN: 25596

South Asian (SAS) AF: 0.00 AC: 0 AN: 27148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2922

European-Non Finnish (NFE) AF: 0.0000429 AC: 40 AN: 932210

Other (OTH) AF: 0.00 AC: 0 AN: 43582

GnomAD4 genome AF: 0.0000332 AC: 5 AN: 150798 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73644

African (AFR) AF: 0.0000243 AC: 1 AN: 41210

American (AMR) AF: 0.00 AC: 0 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5108

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000592 AC: 4 AN: 67524

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ARID1A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Uncertain	0.98
PhyloP100		2.6
PromoterAI		-0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs1039830124; hg19: chr1-27022975;