Genetic Variant NM_001374828.1:c.1229_1234delGAGGAG (chr6-156778889-CGGAGGA-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_001374828.1(ARID1B):c.1229_1234delGAGGAG(p.Gly410_Gly411del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,366,178 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 29)

Exomes 𝑓: 0.0018 ( 12 hom. )

Consequence

ARID1B
NM_001374828.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.18

Publications

0 publications found

Variant links:

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)

ARID1B links:

ENSG00000296922 (HGNC:):

ENSG00000296922 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001374828.1

BP6

Variant 6-156778889-CGGAGGA-C is Benign according to our data. Variant chr6-156778889-CGGAGGA-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 434354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0034 (486/143050) while in subpopulation AMR AF = 0.00522 (76/14550). AF 95% confidence interval is 0.00428. There are 2 homozygotes in GnomAd4. There are 315 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High AC in GnomAd4 at 486 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARID1B	NM_001374828.1	MANE Select	c.1229_1234delGAGGAG	p.Gly410_Gly411del	disruptive_inframe_deletion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
ARID1B	NM_001438482.1		c.1229_1234delGAGGAG	p.Gly410_Gly411del	disruptive_inframe_deletion	Exon 1 of 21	NP_001425411.1
ARID1B	NM_001438483.1		c.1229_1234delGAGGAG	p.Gly410_Gly411del	disruptive_inframe_deletion	Exon 1 of 21	NP_001425412.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.1229_1234delGAGGAG	p.Gly410_Gly411del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
ARID1B	ENST00000346085.10	TSL:1	c.1229_1234delGAGGAG	p.Gly410_Gly411del	disruptive_inframe_deletion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
ARID1B	ENST00000350026.11	TSL:1	c.1229_1234delGAGGAG	p.Gly410_Gly411del	disruptive_inframe_deletion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes

AF:

0.00339

AC:

485

AN:

142976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00296

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00255

Gnomad SAS

AF:

0.00448

Gnomad FIN

AF:

0.0187

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.00102

GnomAD2 exomes

AF:

0.00465

AC:

155

AN:

33354

AF XY:

0.00439

show subpopulations

Gnomad AFR exome

AF:

0.00347

Gnomad AMR exome

AF:

0.00115

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0143

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00185

AC:

2260

AN:

1223128

Hom.:

AF XY:

0.00184

AC XY:

1100

AN XY:

599130

show subpopulations

African (AFR)

AF:

0.00255

AC:

AN:

23952

American (AMR)

AF:

0.00192

AC:

AN:

14562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18608

East Asian (EAS)

AF:

0.00418

AC:

113

AN:

27056

South Asian (SAS)

AF:

0.00283

AC:

149

AN:

52694

European-Finnish (FIN)

AF:

0.0149

AC:

599

AN:

40108

Middle Eastern (MID)

AF:

0.00227

AC:

AN:

4406

European-Non Finnish (NFE)

AF:

0.00123

AC:

1216

AN:

992342

Other (OTH)

AF:

0.00170

AC:

AN:

49400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

102

204

306

408

510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00340

AC:

486

AN:

143050

Hom.:

Cov.:

AF XY:

0.00451

AC XY:

315

AN XY:

69788

show subpopulations

African (AFR)

AF:

0.00301

AC:

117

AN:

38932

American (AMR)

AF:

0.00522

AC:

AN:

14550

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3376

East Asian (EAS)

AF:

0.00256

AC:

AN:

4694

South Asian (SAS)

AF:

0.00450

AC:

AN:

4448

European-Finnish (FIN)

AF:

0.0187

AC:

173

AN:

9254

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.00133

AC:

AN:

64716

Other (OTH)

AF:

0.00101

AC:

AN:

1982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00138

Hom.:

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

ARID1B-related disorder (1)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.2

Mutation Taster

=196/4

polymorphism

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over