rs565325921

Variant names:

• chr1-26695894-T-C
• rs565325921
• XM_047439473.1:c.261A>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The XM_047439473.1(LOC124900417):​c.261A>G​(p.Pro87Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000996 in 1,012,026 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00052 (0 hom.)
• Consequence: LOC124900417 XM_047439473.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0370
• Publications: 0 publications found

Genes affected

LOC124900417 (HGNC:):

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: Labcorp Genetics (formerly Invitae), G2P, Illumina

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-26695894-T-C is Benign according to our data. Variant chr1-26695894-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1219322.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.037 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000521 (448/860256) while in subpopulation AFR AF = 0.0171 (286/16764). AF 95% confidence interval is 0.0154. There are 0 homozygotes in GnomAdExome4. There are 212 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000324856.13. 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.-510T>C		upstream_gene	N/A	NP_006006.3
	ARID1A	NM_139135.4		c.-510T>C		upstream_gene	N/A	NP_624361.1	O14497-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1A	ENST00000457599.7	TSL:5	c.-510T>C		5_prime_UTR	Exon 1 of 20	ENSP00000387636.2	O14497-2
	ARID1A	ENST00000430799.7	TSL:5	c.-13+2277T>C		intron	N/A	ENSP00000390317.3	H0Y488
	ENSG00000260063	ENST00000569378.2	TSL:6	n.50A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00368 AC: 558 AN: 151660 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

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: 0.000339

Gnomad OTH AF: 0.00192

GnomAD4 exome AF: 0.000521 AC: 448 AN: 860256 Hom.: 0 Cov.: 30 AF XY: 0.000534 AC XY: 212 AN XY: 397334

African (AFR) AF: 0.0171 AC: 286 AN: 16764

American (AMR) AF: 0.000614 AC: 1 AN: 1628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6872

East Asian (EAS) AF: 0.00 AC: 0 AN: 9054

South Asian (SAS) AF: 0.00 AC: 0 AN: 16716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 300

Middle Eastern (MID) AF: 0.00446 AC: 8 AN: 1794

European-Non Finnish (NFE) AF: 0.000149 AC: 116 AN: 777610

Other (OTH) AF: 0.00125 AC: 37 AN: 29518

GnomAD4 genome AF: 0.00369 AC: 560 AN: 151770 Hom.: 4 Cov.: 32 AF XY: 0.00354 AC XY: 263 AN XY: 74192

African (AFR) AF: 0.0124 AC: 514 AN: 41456

American (AMR) AF: 0.00124 AC: 19 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

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

European-Non Finnish (NFE) AF: 0.000339 AC: 23 AN: 67822

Other (OTH) AF: 0.00190 AC: 4 AN: 2104

Alfa AF: 0.00277 Hom.: 0

Bravo AF: 0.00437

Asia WGS AF: 0.000582 AC: 2 AN: 3448

ClinVar

ClinVar submissions as Germline

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	-0.75
CADD	Benign	12
DANN	Benign	0.51
PhyloP100		-0.037
PromoterAI		0.012	Neutral

Splicing

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

Other links and lift over

dbSNP: rs565325921; hg19: chr1-27022385;