rs797045274

Variant names:

• chr6-156778283-GCAGCAGCAA-G
• rs797045274
• NM_001374828.1:c.612_620delACAGCAGCA

Your query was ambiguous. Multiple possible variants found:

• chr6-156778283-GCAGCAGCAA-G
• chr6-156778283-GCAGCAGCAA-GCAGCAGCAACAGCAGCAA

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3 BP6 BS2

The NM_001374828.1(ARID1B):​c.612_620delACAGCAGCA​(p.Gln205_Gln207del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000999 in 1,540,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Q204dup) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000092 (0 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:6
• Conservation: PhyloP100: 3.85
• 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

ENSG00000271551 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778283-GCAGCAGCAA-G is Benign according to our data. Variant chr6-156778283-GCAGCAGCAA-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 210285.
• BS2: High AC in GnomAd4 at 26 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	NM_001374828.1	MANE Select	c.612_620delACAGCAGCA	p.Gln205_Gln207del	disruptive_inframe_deletion	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.612_620delACAGCAGCA	p.Gln205_Gln207del	disruptive_inframe_deletion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.612_620delACAGCAGCA	p.Gln205_Gln207del	disruptive_inframe_deletion	Exon 1 of 21	NP_001425412.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.612_620delACAGCAGCA	p.Gln205_Gln207del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.612_620delACAGCAGCA	p.Gln205_Gln207del	disruptive_inframe_deletion	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.612_620delACAGCAGCA	p.Gln205_Gln207del	disruptive_inframe_deletion	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.000172 AC: 26 AN: 151524 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00405

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000738

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000234 AC: 33 AN: 140824 AF XY: 0.000199

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00339

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000386

Gnomad OTH exome AF: 0.000239

GnomAD4 exome AF: 0.0000921 AC: 128 AN: 1389362 Hom.: 0 AF XY: 0.0000846 AC XY: 58 AN XY: 685404

African (AFR) AF: 0.0000636 AC: 2 AN: 31438

American (AMR) AF: 0.00 AC: 0 AN: 35618

Ashkenazi Jewish (ASJ) AF: 0.00323 AC: 81 AN: 25102

East Asian (EAS) AF: 0.00 AC: 0 AN: 35634

South Asian (SAS) AF: 0.0000380 AC: 3 AN: 79042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.0000232 AC: 25 AN: 1076500

Other (OTH) AF: 0.000294 AC: 17 AN: 57768

GnomAD4 genome AF: 0.000172 AC: 26 AN: 151524 Hom.: 0 Cov.: 31 AF XY: 0.000243 AC XY: 18 AN XY: 74000

African (AFR) AF: 0.000145 AC: 6 AN: 41242

American (AMR) AF: 0.0000656 AC: 1 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00405 AC: 14 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000738 AC: 5 AN: 67788

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	ARID1B-related disorder (1)
-	1	-	Coffin-Siris syndrome (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9
Mutation Taster		=172/28	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs797045274; hg19: chr6-157099417;