6-156777927-A-G

Variant names:

• chr6-156777927-A-G
• rs797045266
• NM_001374828.1:c.247A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4 BP6 BS2

The ENST00000636930.2(ARID1B):​c.247A>G​(p.Asn83Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000453 in 1,524,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: ARID1B ENST00000636930.2 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 3.79
• Publications: 1 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

ENSG00000271551 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34527683).
• BP6: Variant 6-156777927-A-G is Benign according to our data. Variant chr6-156777927-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 210264.
• BS2: High AC in GnomAdExome4 at 67 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636930.2. 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.247A>G	p.Asn83Asp	missense	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.247A>G	p.Asn83Asp	missense	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.247A>G	p.Asn83Asp	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.247A>G	p.Asn83Asp	missense	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.247A>G	p.Asn83Asp	missense	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.247A>G	p.Asn83Asp	missense	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 148842 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000161 AC: 2 AN: 124100 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000435

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000487 AC: 67 AN: 1375998 Hom.: 0 Cov.: 34 AF XY: 0.0000398 AC XY: 27 AN XY: 678810

African (AFR) AF: 0.0000321 AC: 1 AN: 31172

American (AMR) AF: 0.00 AC: 0 AN: 34610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24814

East Asian (EAS) AF: 0.00 AC: 0 AN: 35558

South Asian (SAS) AF: 0.00 AC: 0 AN: 78510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4084

European-Non Finnish (NFE) AF: 0.0000576 AC: 62 AN: 1076348

Other (OTH) AF: 0.0000697 AC: 4 AN: 57418

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 148842 Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 2 AN XY: 72646

African (AFR) AF: 0.0000248 AC: 1 AN: 40398

American (AMR) AF: 0.00 AC: 0 AN: 15056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 4950

South Asian (SAS) AF: 0.00 AC: 0 AN: 4716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66824

Other (OTH) AF: 0.00 AC: 0 AN: 2054

Alfa AF: 0.0000480 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.65
CADD	Benign	22
DANN	Benign	0.38
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.35	T
PhyloP100		3.8
GERP RS		2.5
PromoterAI		-0.29	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs797045266; hg19: chr6-157099061;