chr1-26696445-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_006015.6(ARID1A):​c.42C>T​(p.Gly14Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000698 in 1,289,808 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000061 (0 hom.)
• Consequence: ARID1A NM_006015.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 1-26696445-C-T is Benign according to our data. Variant chr1-26696445-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3637045.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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>T	p.Gly14Gly	synonymous	Exon 1 of 20	NP_006006.3
	ARID1A	NM_139135.4		c.42C>T	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>T	p.Gly14Gly	synonymous	Exon 1 of 20	ENSP00000320485.7	O14497-1
	ARID1A	ENST00000850904.1		c.42C>T	p.Gly14Gly	synonymous	Exon 1 of 20	ENSP00000520984.1	A0ABJ7H312
	ARID1A	ENST00000457599.7	TSL:5	c.42C>T	p.Gly14Gly	synonymous	Exon 1 of 20	ENSP00000387636.2	O14497-2

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 147746 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.00690

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000613 AC: 7 AN: 1141948 Hom.: 0 Cov.: 35 AF XY: 0.00000721 AC XY: 4 AN XY: 554460

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

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

Ashkenazi Jewish (ASJ) AF: 0.0000624 AC: 1 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: 0.00000524 AC: 5 AN: 953722

Other (OTH) AF: 0.0000220 AC: 1 AN: 45358

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00199774), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 147860 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 1 AN XY: 72262

African (AFR) AF: 0.00 AC: 0 AN: 40396

American (AMR) AF: 0.00 AC: 0 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3426

East Asian (EAS) AF: 0.00 AC: 0 AN: 4986

South Asian (SAS) AF: 0.00 AC: 0 AN: 4696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9796

Middle Eastern (MID) AF: 0.00719 AC: 2 AN: 278

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66338

Other (OTH) AF: 0.00 AC: 0 AN: 2050

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		1.2
PromoterAI		0.049	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;