1-26696377-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The XM_047439473.1(LOC124900417):c.29G>A(p.Arg10Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00644 in 1,238,348 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0067 (31 hom.)
• Consequence: LOC124900417 XM_047439473.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.512

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 1-26696377-C-T is Benign according to our data. Variant chr1-26696377-C-T is described in ClinVar as [Benign]. Clinvar id is 1226242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124900417	XM_047439473.1	c.29G>A	p.Arg10Lys	missense_variant	1/2
ARID1A	NM_006015.6	c.-27C>T		5_prime_UTR_variant	1/20	ENST00000324856.13
ARID1A	NM_139135.4	c.-27C>T		5_prime_UTR_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1A	ENST00000324856.13	c.-27C>T		5_prime_UTR_variant	1/20	1	NM_006015.6
ARID1A	ENST00000430799.7	c.-13+2760C>T		intron_variant		5		A2
ARID1A	ENST00000637465.1	c.-13+277C>T		intron_variant		5
ARID1A	ENST00000457599.6			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.00415 AC: 613 AN: 147760 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00114

Gnomad AMI AF: 0.00449

Gnomad AMR AF: 0.00247

Gnomad ASJ AF: 0.00995

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00127

Gnomad FIN AF: 0.00102

Gnomad MID AF: 0.00993

Gnomad NFE AF: 0.00697

Gnomad OTH AF: 0.00538

GnomAD3 exomes AF: 0.00534 AC: 9 AN: 1684 Hom.: 0 AF XY: 0.00514 AC XY: 5 AN XY: 972

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00562

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00538

Gnomad NFE exome AF: 0.0114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00675 AC: 7359 AN: 1090472 Hom.: 31 Cov.: 35 AF XY: 0.00669 AC XY: 3485 AN XY: 520884

Gnomad4 AFR exome AF: 0.000854

Gnomad4 AMR exome AF: 0.00334

Gnomad4 ASJ exome AF: 0.00790

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00157

Gnomad4 FIN exome AF: 0.00195

Gnomad4 NFE exome AF: 0.00731

Gnomad4 OTH exome AF: 0.00739

GnomAD4 genome AF: 0.00415 AC: 614 AN: 147876 Hom.: 3 Cov.: 31 AF XY: 0.00403 AC XY: 291 AN XY: 72194

Gnomad4 AFR AF: 0.00114

Gnomad4 AMR AF: 0.00247

Gnomad4 ASJ AF: 0.00995

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00127

Gnomad4 FIN AF: 0.00102

Gnomad4 NFE AF: 0.00697

Gnomad4 OTH AF: 0.00581

Alfa AF: 0.00518 Hom.: 0

Bravo AF: 0.00451

Asia WGS AF: 0.000932 AC: 3 AN: 3234

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 26, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	21
Dann	Benign	0.96

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

Publications

LitVar

Other links and lift over

dbSNP: rs561568918; hg19: chr1-27022868;