rs12199332

Variant names:

• chr6-156822593-G-A
• rs12199332
• NM_001374828.1:c.1792-6634G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001374828.1(ARID1B):​c.1792-6634G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,304 control chromosomes in the GnomAD database, including 1,728 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1728 hom., cov: 33)
• Consequence: ARID1B NM_001374828.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 7 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.1792-6634G>A		intron_variant	Intron 1 of 19	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.1792-6634G>A		intron_variant	Intron 1 of 19	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19905 AN: 152186 Hom.: 1727 Cov.: 33

Gnomad AFR AF: 0.0360

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0669

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.119

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.131 AC: 19909 AN: 152304 Hom.: 1728 Cov.: 33 AF XY: 0.130 AC XY: 9683 AN XY: 74470

African (AFR) AF: 0.0359 AC: 1492 AN: 41576

American (AMR) AF: 0.145 AC: 2226 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3470

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5192

South Asian (SAS) AF: 0.0678 AC: 327 AN: 4822

European-Finnish (FIN) AF: 0.224 AC: 2372 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12634 AN: 68010

Other (OTH) AF: 0.118 AC: 249 AN: 2116

Alfa AF: 0.167 Hom.: 1323

Bravo AF: 0.122

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.66
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12199332; hg19: chr6-157143727; COSMIC: COSV51654306;