6-156779262-GCGCCGCCGC-GCGCCGCCGCCGCCGCCGCCGC

Variant names:

• chr6-156779262-G-GCGCCGCCGCCGC
• rs572236007
• NM_001374828.1:c.1588_1599dupCCGCCGCCGCCG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001374828.1(ARID1B):​c.1588_1599dupCCGCCGCCGCCG​(p.Pro530_Pro533dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000994 in 1,006,140 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S534S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 9.9e-7 (0 hom.)
• Consequence: ARID1B NM_001374828.1 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906
• Publications: 0 publications found

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]

ARID1B Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina, ClinGen
• Coffin-Siris syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000296922 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.1588_1599dupCCGCCGCCGCCG	p.Pro530_Pro533dup	conservative_inframe_insertion	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.1588_1599dupCCGCCGCCGCCG	p.Pro530_Pro533dup	conservative_inframe_insertion	Exon 1 of 20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 9.94e-7 AC: 1 AN: 1006140 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 480486

African (AFR) AF: 0.00 AC: 0 AN: 20280

American (AMR) AF: 0.00 AC: 0 AN: 12724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10068

East Asian (EAS) AF: 0.00 AC: 0 AN: 19772

South Asian (SAS) AF: 0.00 AC: 0 AN: 24952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2664

European-Non Finnish (NFE) AF: 0.00000115 AC: 1 AN: 866174

Other (OTH) AF: 0.00 AC: 0 AN: 36250

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.91

Splicing

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

Other links and lift over

dbSNP: rs572236007; hg19: chr6-157100396;