6-156777718-CGGCGCGGGCGCG-CGGCGCGGGCGCGGGCGCG

Variant names:

• chr6-156777718-C-CGGCGCG
• rs1157870200
• NM_001374828.1:c.54_59dupGCGGGC

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The NM_001374828.1(ARID1B):​c.54_59dupGCGGGC​(p.Ala20_Gly21insArgAla) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000381 in 162,716 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 0.00042 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000056 (0 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.642
• 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: Benign. The variant received -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000421 (61/145004) while in subpopulation EAS AF = 0.00305 (15/4916). AF 95% confidence interval is 0.00188. There are 0 homozygotes in GnomAd4. There are 27 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 61 AD gene.

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.54_59dupGCGGGC	p.Ala20_Gly21insArgAla	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.54_59dupGCGGGC	p.Ala20_Gly21insArgAla	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.54_59dupGCGGGC	p.Ala20_Gly21insArgAla	disruptive_inframe_insertion	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.54_59dupGCGGGC	p.Ala20_Gly21insArgAla	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.54_59dupGCGGGC	p.Ala20_Gly21insArgAla	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.54_59dupGCGGGC	p.Ala20_Gly21insArgAla	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.000421 AC: 61 AN: 145002 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000682

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00304

Gnomad SAS AF: 0.000419

Gnomad FIN AF: 0.000245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000459

Gnomad OTH AF: 0.000505

GnomAD4 exome AF: 0.0000565 AC: 1 AN: 17712 Hom.: 0 Cov.: 2 AF XY: 0.000119 AC XY: 1 AN XY: 8370

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

African (AFR) AF: 0.00 AC: 0 AN: 294

American (AMR) AF: 0.00 AC: 0 AN: 28

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 92

East Asian (EAS) AF: 0.00 AC: 0 AN: 56

South Asian (SAS) AF: 0.00 AC: 0 AN: 448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 30

European-Non Finnish (NFE) AF: 0.0000617 AC: 1 AN: 16214

Other (OTH) AF: 0.00 AC: 0 AN: 544

⚠️ 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: 0.000421 AC: 61 AN: 145004 Hom.: 0 Cov.: 31 AF XY: 0.000383 AC XY: 27 AN XY: 70428

African (AFR) AF: 0.000247 AC: 10 AN: 40536

American (AMR) AF: 0.0000681 AC: 1 AN: 14688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3388

East Asian (EAS) AF: 0.00305 AC: 15 AN: 4916

South Asian (SAS) AF: 0.000422 AC: 2 AN: 4744

European-Finnish (FIN) AF: 0.000245 AC: 2 AN: 8148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.000459 AC: 30 AN: 65416

Other (OTH) AF: 0.000502 AC: 1 AN: 1992

Alfa AF: 0.000123 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.64

Splicing

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

Other links and lift over

dbSNP: rs1157870200; hg19: chr6-157098852;