6-157119916-A-G

Variant names:

• chr6-157119916-A-G
• rs9478751
• NM_001374828.1:c.2581+9355A>G

Variant summary

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

The NM_001374828.1(ARID1B):​c.2581+9355A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,120 control chromosomes in the GnomAD database, including 9,355 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 0.30 (9355 hom., cov: 33)
• Consequence: ARID1B NM_001374828.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548
• Publications: 5 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

ENSG00000233044 (HGNC:40826):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 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.2581+9355A>G		intron	N/A	NP_001361757.1
	ARID1B	NM_001438482.1		c.2581+9355A>G		intron	N/A	NP_001425411.1
	ARID1B	NM_001438483.1		c.2623+9355A>G		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.2581+9355A>G		intron	N/A	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.2620+9355A>G		intron	N/A	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.2581+9355A>G		intron	N/A	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44810 AN: 152002 Hom.: 9335 Cov.: 33

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0142

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.295 AC: 44878 AN: 152120 Hom.: 9355 Cov.: 33 AF XY: 0.286 AC XY: 21289 AN XY: 74382

African (AFR) AF: 0.592 AC: 24548 AN: 41440

American (AMR) AF: 0.198 AC: 3023 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3468

East Asian (EAS) AF: 0.0143 AC: 74 AN: 5190

South Asian (SAS) AF: 0.162 AC: 780 AN: 4824

European-Finnish (FIN) AF: 0.135 AC: 1428 AN: 10598

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13873 AN: 67996

Other (OTH) AF: 0.261 AC: 551 AN: 2114

Alfa AF: 0.232 Hom.: 12913

Bravo AF: 0.311

Asia WGS AF: 0.114 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.5
DANN	Benign	0.88
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: rs9478751; hg19: chr6-157441050; COSMIC: COSV51655596; COSMIC: COSV51655596;