6-156778982-AGGCGGCGGC-AGGCGGCGGCGGC

Variant names:

• chr6-156778982-A-AGGC
• rs797045268
• NM_001374828.1:c.1318_1320dupGGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP3 BP6 BS1 BS2

The NM_001374828.1(ARID1B):​c.1318_1320dupGGC​(p.Gly440dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000928 in 1,262,816 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00078 (2 hom.)
• Consequence: ARID1B NM_001374828.1 conservative_inframe_insertion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:7
• Conservation: PhyloP100: 0.00
• Publications: 1 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

ENSG00000296922 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778982-A-AGGC is Benign according to our data. Variant chr6-156778982-A-AGGC is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 434377.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0021 (289/137404) while in subpopulation AFR AF = 0.00599 (220/36758). AF 95% confidence interval is 0.00534. There are 0 homozygotes in GnomAd4. There are 113 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 289 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.1318_1320dupGGC	p.Gly440dup	conservative_inframe_insertion	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.1318_1320dupGGC	p.Gly440dup	conservative_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.1318_1320dupGGC	p.Gly440dup	conservative_inframe_insertion	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.1318_1320dupGGC	p.Gly440dup	conservative_inframe_insertion	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.1318_1320dupGGC	p.Gly440dup	conservative_inframe_insertion	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.1318_1320dupGGC	p.Gly440dup	conservative_inframe_insertion	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 289 AN: 137298 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00600

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00168

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000240

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000653

Gnomad OTH AF: 0.00160

GnomAD2 exomes AF: 0.00 AC: 0 AN: 1892 AF XY: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000785 AC: 883 AN: 1125412 Hom.: 2 Cov.: 35 AF XY: 0.000731 AC XY: 396 AN XY: 541864

African (AFR) AF: 0.00499 AC: 114 AN: 22846

American (AMR) AF: 0.000714 AC: 6 AN: 8406

Ashkenazi Jewish (ASJ) AF: 0.000415 AC: 6 AN: 14450

East Asian (EAS) AF: 0.00 AC: 0 AN: 26406

South Asian (SAS) AF: 0.000187 AC: 5 AN: 26688

European-Finnish (FIN) AF: 0.0000405 AC: 1 AN: 24706

Middle Eastern (MID) AF: 0.00355 AC: 11 AN: 3096

European-Non Finnish (NFE) AF: 0.000712 AC: 679 AN: 953488

Other (OTH) AF: 0.00135 AC: 61 AN: 45326

GnomAD4 genome AF: 0.00210 AC: 289 AN: 137404 Hom.: 0 Cov.: 29 AF XY: 0.00168 AC XY: 113 AN XY: 67290

African (AFR) AF: 0.00599 AC: 220 AN: 36758

American (AMR) AF: 0.00168 AC: 24 AN: 14254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3284

East Asian (EAS) AF: 0.00 AC: 0 AN: 4272

South Asian (SAS) AF: 0.000240 AC: 1 AN: 4168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 202

European-Non Finnish (NFE) AF: 0.000653 AC: 41 AN: 62784

Other (OTH) AF: 0.00158 AC: 3 AN: 1904

Alfa AF: 0.0000543 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	3	not provided (4)
-	-	2	not specified (2)
-	-	1	ARID1B-related disorder (1)
-	-	1	Inborn genetic diseases (1)
-	1	-	Intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=78/22	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs797045268; hg19: chr6-157100116; COSMIC: COSV51676292; COSMIC: COSV51676292;