chr6-156778665-G-A

Variant names:

• chr6-156778665-G-A
• rs375160616
• NM_001374828.1:c.985G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001374828.1(ARID1B):​c.985G>A​(p.Gly329Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00563 in 1,488,164 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G329A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0047 (1 hom., cov: 30)
  • Exomes 𝑓: 0.0057 (31 hom.)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.438
• Publications: 13 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)

ENSG00000296922 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0049165785).
• BP6: Variant 6-156778665-G-A is Benign according to our data. Variant chr6-156778665-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00472 (708/149844) while in subpopulation AMR AF = 0.00758 (115/15166). AF 95% confidence interval is 0.00646. There are 1 homozygotes in GnomAd4. There are 290 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 708 AD gene.

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.985G>A	p.Gly329Ser	missense	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.985G>A	p.Gly329Ser	missense	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.985G>A	p.Gly329Ser	missense	Exon 1 of 21	NP_001425412.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.985G>A	p.Gly329Ser	missense	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.985G>A	p.Gly329Ser	missense	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.985G>A	p.Gly329Ser	missense	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.00475 AC: 711 AN: 149736 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00119

Gnomad AMI AF: 0.0541

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00905

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00188

Gnomad FIN AF: 0.00138

Gnomad MID AF: 0.0227

Gnomad NFE AF: 0.00628

Gnomad OTH AF: 0.00778

GnomAD2 exomes AF: 0.00477 AC: 471 AN: 98838 AF XY: 0.00460

Gnomad AFR exome AF: 0.000458

Gnomad AMR exome AF: 0.00412

Gnomad ASJ exome AF: 0.0118

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00150

Gnomad NFE exome AF: 0.00652

Gnomad OTH exome AF: 0.00716

GnomAD4 exome AF: 0.00573 AC: 7668 AN: 1338320 Hom.: 31 Cov.: 37 AF XY: 0.00557 AC XY: 3677 AN XY: 660118

African (AFR) AF: 0.00189 AC: 53 AN: 28014

American (AMR) AF: 0.00473 AC: 148 AN: 31268

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 239 AN: 23678

East Asian (EAS) AF: 0.0000329 AC: 1 AN: 30402

South Asian (SAS) AF: 0.00248 AC: 184 AN: 74164

European-Finnish (FIN) AF: 0.00145 AC: 59 AN: 40816

Middle Eastern (MID) AF: 0.0212 AC: 103 AN: 4848

European-Non Finnish (NFE) AF: 0.00625 AC: 6564 AN: 1050108

Other (OTH) AF: 0.00576 AC: 317 AN: 55022

GnomAD4 genome AF: 0.00472 AC: 708 AN: 149844 Hom.: 1 Cov.: 30 AF XY: 0.00396 AC XY: 290 AN XY: 73176

African (AFR) AF: 0.00119 AC: 49 AN: 41126

American (AMR) AF: 0.00758 AC: 115 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.00905 AC: 31 AN: 3426

East Asian (EAS) AF: 0.00 AC: 0 AN: 4948

South Asian (SAS) AF: 0.00188 AC: 9 AN: 4790

European-Finnish (FIN) AF: 0.00138 AC: 14 AN: 10128

Middle Eastern (MID) AF: 0.0208 AC: 6 AN: 288

European-Non Finnish (NFE) AF: 0.00625 AC: 419 AN: 66990

Other (OTH) AF: 0.00771 AC: 16 AN: 2076

Alfa AF: 0.00617 Hom.: 2

Bravo AF: 0.00539

ExAC AF: 0.00315 AC: 46

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not provided (6)
-	-	1	Coffin-Siris syndrome 1 (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.44
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.060
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.50	T
Polyphen		0.0010	B
Vest4		0.12
MVP		0.093
MPC		0.29
ClinPred		0.076	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.19
gMVP		0.13
Mutation Taster		=100/0	polymorphism

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: rs375160616; hg19: chr6-157099799; COSMIC: COSV51664851; COSMIC: COSV51664851;