Genetic Variant ARID1B:p.Pro532_Pro533dup (chr6-156779262-G-GCGCCGC) – 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.1594_1599dupCCGCCG(p.Pro532_Pro533dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,146,124 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S534S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

ARID1B
NM_001374828.1 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.906

Publications

6 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, Orphanet, ClinGen
Coffin-Siris syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

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 6-156779262-G-GCGCCGC is Benign according to our data. Variant chr6-156779262-G-GCGCCGC is described in ClinVar as Likely_benign. ClinVar VariationId is 1936461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000729 (102/139986) while in subpopulation AFR AF = 0.00237 (92/38822). AF 95% confidence interval is 0.00198. There are 0 homozygotes in GnomAd4. There are 49 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.

BS2

High AC in GnomAd4 at 102 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.1594_1599dupCCGCCG	p.Pro532_Pro533dup	conservative_inframe_insertion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
ARID1B	NM_001438482.1		c.1594_1599dupCCGCCG	p.Pro532_Pro533dup	conservative_inframe_insertion	Exon 1 of 21	NP_001425411.1
ARID1B	NM_001438483.1		c.1594_1599dupCCGCCG	p.Pro532_Pro533dup	conservative_inframe_insertion	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.1594_1599dupCCGCCG	p.Pro532_Pro533dup	conservative_inframe_insertion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
ARID1B	ENST00000346085.10	TSL:1	c.1594_1599dupCCGCCG	p.Pro532_Pro533dup	conservative_inframe_insertion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
ARID1B	ENST00000350026.11	TSL:1	c.1594_1599dupCCGCCG	p.Pro532_Pro533dup	conservative_inframe_insertion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes

AF:

0.000729

AC:

102

AN:

139874

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00238

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000483

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:

0.0000475

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000616

AC:

AN:

64972

AF XY:

0.0000266

show subpopulations

Gnomad AFR exome

AF:

0.000672

Gnomad AMR exome

AF:

0.000127

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:

0.0000686

AC:

AN:

1006138

Hom.:

Cov.:

AF XY:

0.0000479

AC XY:

AN XY:

480486

show subpopulations

African (AFR)

AF:

0.00187

AC:

AN:

20280

American (AMR)

AF:

0.0000786

AC:

AN:

12724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10068

East Asian (EAS)

AF:

0.00

AC:

AN:

19772

South Asian (SAS)

AF:

0.00

AC:

AN:

24952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2664

European-Non Finnish (NFE)

AF:

0.0000335

AC:

AN:

866172

Other (OTH)

AF:

0.0000276

AC:

AN:

36250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000729

AC:

102

AN:

139986

Hom.:

Cov.:

AF XY:

0.000719

AC XY:

AN XY:

68130

show subpopulations

African (AFR)

AF:

0.00237

AC:

AN:

38822

American (AMR)

AF:

0.000482

AC:

AN:

14508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3318

East Asian (EAS)

AF:

0.00

AC:

AN:

4508

South Asian (SAS)

AF:

0.00

AC:

AN:

4532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000475

AC:

AN:

63212

Other (OTH)

AF:

0.00

AC:

AN:

1948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.91

Mutation Taster

=88/12

polymorphism

(source)

Splicing

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

Publications

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6-156779262-GCGCCGCCGC-GCGCCGCCGCCGCCGC

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