6-156822736-G-C

Variant names:

• chr6-156822736-G-C
• rs176375
• NM_001374828.1:c.1792-6491G>C

Variant summary

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

The NM_001374828.1(ARID1B):​c.1792-6491G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,174 control chromosomes in the GnomAD database, including 2,723 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 0.18 (2723 hom., cov: 32)
• Consequence: ARID1B NM_001374828.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 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.1792-6491G>C		intron	N/A	NP_001361757.1
	ARID1B	NM_001438482.1		c.1792-6491G>C		intron	N/A	NP_001425411.1
	ARID1B	NM_001438483.1		c.1792-6491G>C		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.1792-6491G>C		intron	N/A	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.1792-6491G>C		intron	N/A	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.1792-6491G>C		intron	N/A	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27362 AN: 152056 Hom.: 2720 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.180 AC: 27380 AN: 152174 Hom.: 2723 Cov.: 32 AF XY: 0.174 AC XY: 12948 AN XY: 74408

African (AFR) AF: 0.176 AC: 7315 AN: 41520

American (AMR) AF: 0.133 AC: 2042 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 602 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5190

South Asian (SAS) AF: 0.145 AC: 699 AN: 4810

European-Finnish (FIN) AF: 0.120 AC: 1274 AN: 10598

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14605 AN: 67966

Other (OTH) AF: 0.190 AC: 402 AN: 2112

Alfa AF: 0.108 Hom.: 166

Bravo AF: 0.180

Asia WGS AF: 0.0600 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.56
PhyloP100		-2.4
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: rs176375; hg19: chr6-157143870;