rs751352361

Variant names:

• chr1-26697417-GGCTGCGGCGGCGGCA-G
• rs751352361
• NM_006015.6:c.1029_1043delAGCTGCGGCGGCGGC

Your query was ambiguous. Multiple possible variants found:

• chr1-26697417-GGCTGCGGCGGCGGCA-G
• chr1-26697417-GGCTGCGGCGGCGGCA-GGCTGCGGCGGCGGCAGCTGCGGCGGCGGCA

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The NM_006015.6(ARID1A):​c.1029_1043delAGCTGCGGCGGCGGC​(p.Ala344_Ala348del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000626 in 1,350,944 control chromosomes in the GnomAD database, including 4 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00083 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (4 hom.)
• Consequence: ARID1A NM_006015.6 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.51
• Publications: 1 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

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_006015.6
• BP6: Variant 1-26697417-GGCTGCGGCGGCGGCA-G is Benign according to our data. Variant chr1-26697417-GGCTGCGGCGGCGGCA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 434336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00083 (126/151816) while in subpopulation SAS AF = 0.00208 (10/4810). AF 95% confidence interval is 0.00113. There are 0 homozygotes in GnomAd4. There are 60 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 126 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.1029_1043delAGCTGCGGCGGCGGC	p.Ala344_Ala348del	disruptive_inframe_deletion	Exon 1 of 20	NP_006006.3
	ARID1A	NM_139135.4		c.1029_1043delAGCTGCGGCGGCGGC	p.Ala344_Ala348del	disruptive_inframe_deletion	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.1029_1043delAGCTGCGGCGGCGGC	p.Ala344_Ala348del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000320485.7	O14497-1
	ARID1A	ENST00000850904.1		c.1029_1043delAGCTGCGGCGGCGGC	p.Ala344_Ala348del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000520984.1	A0ABJ7H312
	ARID1A	ENST00000457599.7	TSL:5	c.1029_1043delAGCTGCGGCGGCGGC	p.Ala344_Ala348del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000387636.2	O14497-2

Frequencies

GnomAD3 genomes AF: 0.000831 AC: 126 AN: 151700 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000895

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00116

Gnomad EAS AF: 0.000782

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000766

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00275 AC: 3 AN: 1092 AF XY: 0.00442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000600 AC: 720 AN: 1199128 Hom.: 4 AF XY: 0.000588 AC XY: 343 AN XY: 583532

African (AFR) AF: 0.000886 AC: 21 AN: 23700

American (AMR) AF: 0.000999 AC: 9 AN: 9006

Ashkenazi Jewish (ASJ) AF: 0.000554 AC: 9 AN: 16246

East Asian (EAS) AF: 0.000904 AC: 25 AN: 27642

South Asian (SAS) AF: 0.00181 AC: 85 AN: 46922

European-Finnish (FIN) AF: 0.000250 AC: 7 AN: 27950

Middle Eastern (MID) AF: 0.000302 AC: 1 AN: 3312

European-Non Finnish (NFE) AF: 0.000522 AC: 519 AN: 995074

Other (OTH) AF: 0.000893 AC: 44 AN: 49276

GnomAD4 genome AF: 0.000830 AC: 126 AN: 151816 Hom.: 0 Cov.: 32 AF XY: 0.000809 AC XY: 60 AN XY: 74192

African (AFR) AF: 0.000892 AC: 37 AN: 41460

American (AMR) AF: 0.00105 AC: 16 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 4 AN: 3462

East Asian (EAS) AF: 0.000785 AC: 4 AN: 5096

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4810

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000767 AC: 52 AN: 67834

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000162 Hom.: 0

Bravo AF: 0.000884

Asia WGS AF: 0.00174 AC: 6 AN: 3458

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	ARID1A-related disorder (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	Intellectual disability, autosomal dominant 14 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=185/15	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs751352361; hg19: chr1-27023908; COSMIC: COSV61371577; COSMIC: COSV61371577;