rs6917698

Variant names:

• chr6-157122219-A-G
• rs6917698
• NM_001374828.1:c.2582-10809A>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.2582-10809A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,172 control chromosomes in the GnomAD database, including 2,869 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 (2869 hom., cov: 32)
• Consequence: ARID1B NM_001374828.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• 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: Illumina, ClinGen, Orphanet
• Coffin-Siris syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

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 (AMR) allele frequency at 95% confidence interval = 0.222 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	NM_001374828.1	MANE Select	c.2582-10809A>G		intron	N/A	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.2582-10809A>G		intron	N/A	NP_001425411.1
	ARID1B	NM_001438483.1		c.2624-10809A>G		intron	N/A	NP_001425412.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.2582-10809A>G		intron	N/A	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.2621-10809A>G		intron	N/A	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.2582-10809A>G		intron	N/A	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27239 AN: 152054 Hom.: 2871 Cov.: 32

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.179 AC: 27238 AN: 152172 Hom.: 2869 Cov.: 32 AF XY: 0.180 AC XY: 13389 AN XY: 74378

African (AFR) AF: 0.0671 AC: 2784 AN: 41514

American (AMR) AF: 0.229 AC: 3496 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3464

East Asian (EAS) AF: 0.217 AC: 1124 AN: 5180

South Asian (SAS) AF: 0.191 AC: 921 AN: 4820

European-Finnish (FIN) AF: 0.253 AC: 2673 AN: 10576

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14822 AN: 68006

Other (OTH) AF: 0.204 AC: 431 AN: 2112

Alfa AF: 0.205 Hom.: 804

Bravo AF: 0.176

Asia WGS AF: 0.163 AC: 565 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	0.0030
DANN	Benign	0.23
PhyloP100		-1.8
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: rs6917698; hg19: chr6-157443353; COSMIC: COSV51678401; COSMIC: COSV51678401;