chr6-156779412-C-A

Variant names:

• chr6-156779412-C-A
• rs1554248236
• NM_001374828.1:c.1732C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001374828.1(ARID1B):​c.1732C>A​(p.Gln578Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000762 in 1,312,740 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: 31)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.27
• 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

ENSG00000296922 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26568985).

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.1732C>A	p.Gln578Lys	missense	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.1732C>A	p.Gln578Lys	missense	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.1732C>A	p.Gln578Lys	missense	Exon 1 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.1732C>A	p.Gln578Lys	missense	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.1732C>A	p.Gln578Lys	missense	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.1732C>A	p.Gln578Lys	missense	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.62e-7 AC: 1 AN: 1312740 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 653162

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27082

American (AMR) AF: 0.00 AC: 0 AN: 32218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21790

East Asian (EAS) AF: 0.00 AC: 0 AN: 29050

South Asian (SAS) AF: 0.00 AC: 0 AN: 74738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4770

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1038040

Other (OTH) AF: 0.0000192 AC: 1 AN: 52130

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.093
Eigen_PC	Benign	-0.067
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.3
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.53	T
Polyphen		0.61	P
Vest4		0.21
MutPred		0.34		Gain of methylation at Q495 (P = 1e-04)
MVP		0.44
MPC		0.82
ClinPred		0.89	D
GERP RS		3.0
PromoterAI		-0.11	Neutral
Varity_R		0.31
gMVP		0.23
Mutation Taster		=74/26	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: rs1554248236; hg19: chr6-157100546;