chr6-156778292-A-ACAGCAG

Variant names:

• chr6-156778292-A-ACAGCAG
• rs587779744
• NM_001374828.1:c.630_635dupGCAGCA

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The NM_001374828.1(ARID1B):​c.630_635dupGCAGCA​(p.Gln211_Gln212dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00713 in 145,394 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q212Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0071 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0079 (27 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.46
• Publications: 12 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 -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778292-A-ACAGCAG is Benign according to our data. Variant chr6-156778292-A-ACAGCAG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 126329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00713 (1037/145394) while in subpopulation NFE AF = 0.00927 (623/67172). AF 95% confidence interval is 0.00867. There are 5 homozygotes in GnomAd4. There are 454 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1037 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.630_635dupGCAGCA	p.Gln211_Gln212dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.630_635dupGCAGCA	p.Gln211_Gln212dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.630_635dupGCAGCA	p.Gln211_Gln212dup	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.630_635dupGCAGCA	p.Gln211_Gln212dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.630_635dupGCAGCA	p.Gln211_Gln212dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.630_635dupGCAGCA	p.Gln211_Gln212dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.00714 AC: 1038 AN: 145294 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00614

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.00468

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.000403

Gnomad SAS AF: 0.00168

Gnomad FIN AF: 0.00727

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00929

Gnomad OTH AF: 0.00651

GnomAD2 exomes AF: 0.00494 AC: 624 AN: 126374 AF XY: 0.00479

Gnomad AFR exome AF: 0.00368

Gnomad AMR exome AF: 0.00524

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000212

Gnomad FIN exome AF: 0.00425

Gnomad NFE exome AF: 0.00859

Gnomad OTH exome AF: 0.00585

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00789 AC: 10833 AN: 1372320 Hom.: 27 Cov.: 37 AF XY: 0.00757 AC XY: 5128 AN XY: 677498

African (AFR) AF: 0.00503 AC: 141 AN: 28036

American (AMR) AF: 0.00528 AC: 185 AN: 35064

Ashkenazi Jewish (ASJ) AF: 0.0000806 AC: 2 AN: 24812

East Asian (EAS) AF: 0.000144 AC: 5 AN: 34776

South Asian (SAS) AF: 0.000968 AC: 76 AN: 78520

European-Finnish (FIN) AF: 0.00508 AC: 216 AN: 42484

Middle Eastern (MID) AF: 0.00181 AC: 10 AN: 5526

European-Non Finnish (NFE) AF: 0.00922 AC: 9836 AN: 1066296

Other (OTH) AF: 0.00637 AC: 362 AN: 56806

GnomAD4 genome AF: 0.00713 AC: 1037 AN: 145394 Hom.: 5 Cov.: 31 AF XY: 0.00638 AC XY: 454 AN XY: 71142

African (AFR) AF: 0.00612 AC: 223 AN: 36448

American (AMR) AF: 0.00467 AC: 70 AN: 14984

Ashkenazi Jewish (ASJ) AF: 0.000293 AC: 1 AN: 3414

East Asian (EAS) AF: 0.000405 AC: 2 AN: 4942

South Asian (SAS) AF: 0.00168 AC: 8 AN: 4770

European-Finnish (FIN) AF: 0.00727 AC: 76 AN: 10448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00927 AC: 623 AN: 67172

Other (OTH) AF: 0.00644 AC: 13 AN: 2020

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=77/23	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs587779744; hg19: chr6-157099426; COSMIC: COSV51649063; COSMIC: COSV51649063;