chr6-156777818-CGCG-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP3 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
• 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: Illumina, ClinGen, Orphanet
• Coffin-Siris syndrome 1

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

ENSG00000271551 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374828.1. 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
	ARID1B	NM_001374828.1	MANE Select	c.156_158delGGC	p.Ala53del	disruptive_inframe_deletion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.156_158delGGC	p.Ala53del	disruptive_inframe_deletion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.156_158delGGC	p.Ala53del	disruptive_inframe_deletion	Exon 1 of 21	NP_001425412.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.156_158delGGC	p.Ala53del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.156_158delGGC	p.Ala53del	disruptive_inframe_deletion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.156_158delGGC	p.Ala53del	disruptive_inframe_deletion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00143 AC: 24 AN: 16750

American (AMR) AF: 0.00311 AC: 7 AN: 2250

Ashkenazi Jewish (ASJ) AF: 0.00216 AC: 14 AN: 6490

East Asian (EAS) AF: 0.00573 AC: 39 AN: 6804

South Asian (SAS) AF: 0.00110 AC: 19 AN: 17334

European-Finnish (FIN) AF: 0.00808 AC: 36 AN: 4456

Middle Eastern (MID) AF: 0.00165 AC: 3 AN: 1822

European-Non Finnish (NFE) AF: 0.000916 AC: 709 AN: 774354

Other (OTH) AF: 0.00136 AC: 40 AN: 29520

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.000101 AC: 4 AN: 39434

American (AMR) AF: 0.00 AC: 0 AN: 14520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3358

East Asian (EAS) AF: 0.00 AC: 0 AN: 4832

South Asian (SAS) AF: 0.000215 AC: 1 AN: 4650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000466 AC: 3 AN: 64310

Other (OTH) AF: 0.00 AC: 0 AN: 1952

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49

Splicing

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

Other links and lift over

dbSNP: rs1046394316; hg19: chr6-157098952;