NM_001374828.1:c.2137-5257G>A

Variant names:

• chr6-156930209-G-A
• rs185866
• NM_001374828.1:c.2137-5257G>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.2137-5257G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,142 control chromosomes in the GnomAD database, including 1,115 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 0.11 (1115 hom., cov: 32)
• Consequence: ARID1B NM_001374828.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.553
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

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.2137-5257G>A		intron	N/A	NP_001361757.1
	ARID1B	NM_001438482.1		c.2137-5257G>A		intron	N/A	NP_001425411.1
	ARID1B	NM_001438483.1		c.2137-5257G>A		intron	N/A	NP_001425412.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.2137-5257G>A		intron	N/A	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.2176-5257G>A		intron	N/A	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.2137-5257G>A		intron	N/A	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17232 AN: 152024 Hom.: 1109 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0241

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0729

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.113 AC: 17247 AN: 152142 Hom.: 1115 Cov.: 32 AF XY: 0.111 AC XY: 8256 AN XY: 74380

African (AFR) AF: 0.155 AC: 6433 AN: 41468

American (AMR) AF: 0.0783 AC: 1198 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3470

East Asian (EAS) AF: 0.0244 AC: 126 AN: 5172

South Asian (SAS) AF: 0.120 AC: 577 AN: 4816

European-Finnish (FIN) AF: 0.0729 AC: 773 AN: 10602

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7146 AN: 68002

Other (OTH) AF: 0.107 AC: 227 AN: 2112

Alfa AF: 0.0437 Hom.: 31

Bravo AF: 0.113

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.77
PhyloP100		-0.55
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: rs185866; hg19: chr6-157251343;