NM_001374828.1:c.6916C>G

Variant names:

• chr6-157207688-C-G
• rs1308155037
• NM_001374828.1:c.6916C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001374828.1(ARID1B):​c.6916C>G​(p.Gln2306Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000755 in 1,456,698 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.51
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25010955).
• BS2: High AC in GnomAdExome4 at 11 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	NM_001374828.1	MANE Select	c.6916C>G	p.Gln2306Glu	missense	Exon 20 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.7045C>G	p.Gln2349Glu	missense	Exon 21 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.6958C>G	p.Gln2320Glu	missense	Exon 21 of 21	NP_001425412.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.6916C>G	p.Gln2306Glu	missense	Exon 20 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.6796C>G	p.Gln2266Glu	missense	Exon 21 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.6757C>G	p.Gln2253Glu	missense	Exon 19 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000755 AC: 11 AN: 1456698 Hom.: 0 Cov.: 31 AF XY: 0.00000967 AC XY: 7 AN XY: 723524

African (AFR) AF: 0.00 AC: 0 AN: 33400

American (AMR) AF: 0.00 AC: 0 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.00 AC: 0 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000903 AC: 10 AN: 1107688

Other (OTH) AF: 0.0000166 AC: 1 AN: 60108

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.14
Sift	Uncertain	0.011	D
Sift4G	Benign	0.069	T
Polyphen		0.99	D
Vest4		0.56
MutPred		0.14		Loss of helix (P = 0.0376)
MVP		0.49
MPC		1.5
ClinPred		0.59	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.20
gMVP		0.48
Mutation Taster		=79/21	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: rs1308155037; hg19: chr6-157528822;