6-156777818-CGCGGCGGCGGCG-CGCGGCGGCG

Variant names:

• chr6-156777818-CGCG-C
• rs1046394316
• NM_001374828.1:c.156_158delGGC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3 BS1 BS2_Supporting

The NM_001374828.1(ARID1B):​c.156_158delGGC​(p.Ala53del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000897 in 1,002,008 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000056 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490

Genes affected

ARID1B (HGNC:18040): (AT-rich interaction domain 1B) This locus encodes an AT-rich DNA interacting domain-containing protein. The encoded protein is a component of the SWI/SNF chromatin remodeling complex and may play a role in cell-cycle activation. The protein encoded by this locus is similar to AT-rich interactive domain-containing protein 1A. These two proteins function as alternative, mutually exclusive ARID-subunits of the SWI/SNF complex. The associated complexes play opposing roles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ENSG00000271551 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00104 (891/859780) while in subpopulation EAS AF= 0.00573 (39/6804). AF 95% confidence interval is 0.00431. There are 0 homozygotes in gnomad4_exome. There are 422 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 8 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.156_158delGGC	p.Ala53del	disruptive_inframe_deletion	Exon 1 of 20	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.156_158delGGC	p.Ala53del	disruptive_inframe_deletion	Exon 1 of 20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes AF: 0.0000562 AC: 8 AN: 142228 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000466

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00104 AC: 891 AN: 859780 Hom.: 0 AF XY: 0.00105 AC XY: 422 AN XY: 400222

Gnomad4 AFR exome AF: 0.00143

Gnomad4 AMR exome AF: 0.00311

Gnomad4 ASJ exome AF: 0.00216

Gnomad4 EAS exome AF: 0.00573

Gnomad4 SAS exome AF: 0.00110

Gnomad4 FIN exome AF: 0.00808

Gnomad4 NFE exome AF: 0.000916

Gnomad4 OTH exome AF: 0.00136

GnomAD4 genome AF: 0.0000562 AC: 8 AN: 142228 Hom.: 0 Cov.: 30 AF XY: 0.0000289 AC XY: 2 AN XY: 69132

Gnomad4 AFR AF: 0.000101

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000215

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000466

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1046394316; hg19: chr6-157098952;