rs797045268

Positions:

• chr6-156778982-AGGCGGCGGC-A
• chr6-156778982-AGGCGGCGGC-AGGC
• chr6-156778982-AGGCGGCGGC-AGGCGGC
• chr6-156778982-AGGCGGCGGC-AGGCGGCGGCGGC
• chr6-156778982-AGGCGGCGGC-AGGCGGCGGCGGCGGC
• chr6-156778982-AGGCGGCGGC-AGGCGGCGGCGGCGGCGGC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3 BS2

The NM_001374828.1(ARID1B):​c.1312_1320del​(p.Gly438_Gly440del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,262,838 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000036 (1 hom.)
• Consequence: ARID1B NM_001374828.1 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.82

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BS2: High AC in GnomAdExome4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.1312_1320del	p.Gly438_Gly440del	inframe_deletion	1/20	ENST00000636930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.1312_1320del	p.Gly438_Gly440del	inframe_deletion	1/20	2	NM_001374828.1	A2

Frequencies

GnomAD3 genomes AF: 0.0000146 AC: 2 AN: 137298 Hom.: 0 Cov.: 29

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: 0.00

Gnomad NFE AF: 0.0000319

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000364 AC: 41 AN: 1125434 Hom.: 1 AF XY: 0.0000461 AC XY: 25 AN XY: 541872

Gnomad4 AFR exome AF: 0.0000438

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000399

Gnomad4 OTH exome AF: 0.0000441

GnomAD4 genome AF: 0.0000146 AC: 2 AN: 137404 Hom.: 0 Cov.: 29 AF XY: 0.0000297 AC XY: 2 AN XY: 67288

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000319

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2023

This variant, c.1063_1071del, results in the deletion of 3 amino acid(s) of the ARID1B protein (p.Gly355_Gly357del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ARID1B-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

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: rs797045268; hg19: chr6-157100116;