chr6-156777718-C-CGGCGCGGGCGCG

Variant names:

• chr6-156777718-C-CGGCGCGGGCGCG
• rs1157870200
• NM_001374828.1:c.48_59dupGCGGGCGCGGGC

Variant summary

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

The NM_001374828.1(ARID1B):​c.48_59dupGCGGGCGCGGGC​(p.Ala20_Gly21insArgAlaArgAla) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 145,002 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.

• Frequency: Genomes: 𝑓 0.000014 (0 hom., cov: 31)
• 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: Likely_benign. The variant received -1 ACMG points.

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

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.48_59dupGCGGGCGCGGGC	p.Ala20_Gly21insArgAlaArgAla	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.48_59dupGCGGGCGCGGGC	p.Ala20_Gly21insArgAlaArgAla	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.48_59dupGCGGGCGCGGGC	p.Ala20_Gly21insArgAlaArgAla	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.48_59dupGCGGGCGCGGGC	p.Ala20_Gly21insArgAlaArgAla	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.48_59dupGCGGGCGCGGGC	p.Ala20_Gly21insArgAlaArgAla	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.48_59dupGCGGGCGCGGGC	p.Ala20_Gly21insArgAlaArgAla	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.0000138 AC: 2 AN: 145002 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000494

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 2

GnomAD4 genome AF: 0.0000138 AC: 2 AN: 145002 Hom.: 0 Cov.: 31 AF XY: 0.0000142 AC XY: 1 AN XY: 70410

African (AFR) AF: 0.0000494 AC: 2 AN: 40476

American (AMR) AF: 0.00 AC: 0 AN: 14672

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4936

South Asian (SAS) AF: 0.00 AC: 0 AN: 4770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65428

Other (OTH) AF: 0.00 AC: 0 AN: 1982

Alfa AF: 0.00 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;