NM_001374828.1:c.1247_1255dupGAGCAGGAG

Variant names:

• chr6-156778915-C-CAGGAGCAGG
• rs771557031
• NM_001374828.1:c.1247_1255dupGAGCAGGAG

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_001374828.1(ARID1B):​c.1247_1255dupGAGCAGGAG​(p.Gly416_Gly418dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000641 in 140,340 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000064 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000025 (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: 0.00900
• 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

ENSG00000296922 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778915-C-CAGGAGCAGG is Benign according to our data. Variant chr6-156778915-C-CAGGAGCAGG is described in ClinVar as Likely_benign. ClinVar VariationId is 2138273.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 9 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.1247_1255dupGAGCAGGAG	p.Gly416_Gly418dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.1247_1255dupGAGCAGGAG	p.Gly416_Gly418dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.1247_1255dupGAGCAGGAG	p.Gly416_Gly418dup	disruptive_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.1247_1255dupGAGCAGGAG	p.Gly416_Gly418dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.1247_1255dupGAGCAGGAG	p.Gly416_Gly418dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.1247_1255dupGAGCAGGAG	p.Gly416_Gly418dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.0000641 AC: 9 AN: 140340 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000105

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: 0.0000627

Gnomad OTH AF: 0.000521

GnomAD2 exomes AF: 0.00 AC: 0 AN: 18646 AF XY: 0.00

Gnomad AFR exome AF: 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000245 AC: 29 AN: 1181910 Hom.: 0 Cov.: 35 AF XY: 0.0000174 AC XY: 10 AN XY: 575626

African (AFR) AF: 0.000128 AC: 3 AN: 23442

American (AMR) AF: 0.00 AC: 0 AN: 10396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16712

East Asian (EAS) AF: 0.0000411 AC: 1 AN: 24310

South Asian (SAS) AF: 0.00 AC: 0 AN: 43118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3854

European-Non Finnish (NFE) AF: 0.0000246 AC: 24 AN: 976122

Other (OTH) AF: 0.0000209 AC: 1 AN: 47796

GnomAD4 genome AF: 0.0000641 AC: 9 AN: 140340 Hom.: 0 Cov.: 30 AF XY: 0.0000584 AC XY: 4 AN XY: 68548

African (AFR) AF: 0.000105 AC: 4 AN: 37996

American (AMR) AF: 0.00 AC: 0 AN: 14292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3320

East Asian (EAS) AF: 0.00 AC: 0 AN: 4372

South Asian (SAS) AF: 0.00 AC: 0 AN: 4364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 248

European-Non Finnish (NFE) AF: 0.0000627 AC: 4 AN: 63840

Other (OTH) AF: 0.000521 AC: 1 AN: 1918

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0090
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: rs771557031; hg19: chr6-157100049;