Genetic Variant ARID1B:p.Ala13_Ala14del (chr6-156777698-AGCGGCG-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3BS1BS2

The NM_001374828.1(ARID1B):c.37_42delGCGGCG(p.Ala13_Ala14del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 146,742 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0019 ( 1 hom. )

Consequence

ARID1B
NM_001374828.1 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.19

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:

ENSG00000271551 (HGNC:):

ENSG00000271551 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001374828.1

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00152 (218/143580) while in subpopulation NFE AF = 0.00128 (83/65064). AF 95% confidence interval is 0.00105. There are 0 homozygotes in GnomAd4. There are 147 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 218 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.37_42delGCGGCG	p.Ala13_Ala14del	conservative_inframe_deletion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
ARID1B	NM_001438482.1		c.37_42delGCGGCG	p.Ala13_Ala14del	conservative_inframe_deletion	Exon 1 of 21	NP_001425411.1
ARID1B	NM_001438483.1		c.37_42delGCGGCG	p.Ala13_Ala14del	conservative_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.37_42delGCGGCG	p.Ala13_Ala14del	conservative_inframe_deletion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
ARID1B	ENST00000346085.10	TSL:1	c.37_42delGCGGCG	p.Ala13_Ala14del	conservative_inframe_deletion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
ARID1B	ENST00000350026.11	TSL:1	c.37_42delGCGGCG	p.Ala13_Ala14del	conservative_inframe_deletion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes

AF:

0.00152

AC:

218

AN:

143528

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000401

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000687

Gnomad ASJ

AF:

0.000297

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000654

Gnomad FIN

AF:

0.0128

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.000504

GnomAD4 exome

AF:

0.00190

AC:

AN:

3162

Hom.:

AF XY:

0.00134

AC XY:

AN XY:

1498

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00221

AC:

AN:

2710

Other (OTH)

AF:

0.00

AC:

AN:

124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.588

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00152

AC:

218

AN:

143580

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

147

AN XY:

69816

show subpopulations

African (AFR)

AF:

0.000400

AC:

AN:

39986

American (AMR)

AF:

0.000686

AC:

AN:

14570

Ashkenazi Jewish (ASJ)

AF:

0.000297

AC:

AN:

3364

East Asian (EAS)

AF:

0.00

AC:

AN:

4742

South Asian (SAS)

AF:

0.000655

AC:

AN:

4582

European-Finnish (FIN)

AF:

0.0128

AC:

104

AN:

8106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.00128

AC:

AN:

65064

Other (OTH)

AF:

0.000500

AC:

AN:

2002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.000779

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

Splicing

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

Publications

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6-156777698-AGCGGCGGCGGCGGCG-AGCGGCGGCG

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