NM_001374828.1:c.612_623dupACAGCAGCAGCA

Variant names:

• chr6-156778280-G-GCAGCAGCAGCAA
• rs797045275
• NM_001374828.1:c.612_623dupACAGCAGCAGCA

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP3 BP6_Moderate

The NM_001374828.1(ARID1B):​c.612_623dupACAGCAGCAGCA​(p.Gln205_Gln208dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. Q208Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000072 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.751
• Publications: 2 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 -3 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778280-G-GCAGCAGCAGCAA is Benign according to our data. Variant chr6-156778280-G-GCAGCAGCAGCAA is described in ClinVar as Likely_benign. ClinVar VariationId is 2308673.Status of the report is criteria_provided_single_submitter, 1 stars.

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.612_623dupACAGCAGCAGCA	p.Gln205_Gln208dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.612_623dupACAGCAGCAGCA	p.Gln205_Gln208dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.612_623dupACAGCAGCAGCA	p.Gln205_Gln208dup	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.612_623dupACAGCAGCAGCA	p.Gln205_Gln208dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.612_623dupACAGCAGCAGCA	p.Gln205_Gln208dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.612_623dupACAGCAGCAGCA	p.Gln205_Gln208dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000285 AC: 4 AN: 140422 AF XY: 0.0000266

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000280

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000193

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000720 AC: 10 AN: 1389726 Hom.: 0 Cov.: 37 AF XY: 0.0000102 AC XY: 7 AN XY: 685572

African (AFR) AF: 0.00 AC: 0 AN: 31476

American (AMR) AF: 0.00 AC: 0 AN: 35640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25092

East Asian (EAS) AF: 0.0000842 AC: 3 AN: 35636

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 79048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5618

European-Non Finnish (NFE) AF: 0.00000557 AC: 6 AN: 1077016

Other (OTH) AF: 0.00 AC: 0 AN: 57800

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.75
Mutation Taster		=74/26	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs797045275; hg19: chr6-157099414;