chr6-156777818-CGCGGCGGCG-C

Variant names:

• chr6-156777818-CGCGGCGGCG-C
• rs1046394316
• NM_001374828.1:c.150_158delGGCGGCGGC

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The NM_001374828.1(ARID1B):​c.150_158delGGCGGCGGC​(p.Ala51_Ala53del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,011,732 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28
• 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: Illumina, ClinGen, Orphanet
• Coffin-Siris syndrome 1

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

ENSG00000271551 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000253 (36/142226) while in subpopulation EAS AF = 0.000414 (2/4832). AF 95% confidence interval is 0.000231. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 36 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.150_158delGGCGGCGGC	p.Ala51_Ala53del	disruptive_inframe_deletion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.150_158delGGCGGCGGC	p.Ala51_Ala53del	disruptive_inframe_deletion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.150_158delGGCGGCGGC	p.Ala51_Ala53del	disruptive_inframe_deletion	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.150_158delGGCGGCGGC	p.Ala51_Ala53del	disruptive_inframe_deletion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.150_158delGGCGGCGGC	p.Ala51_Ala53del	disruptive_inframe_deletion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.150_158delGGCGGCGGC	p.Ala51_Ala53del	disruptive_inframe_deletion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.000253 AC: 36 AN: 142226 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000414

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000342

Gnomad OTH AF: 0.000512

GnomAD4 exome AF: 0.000247 AC: 215 AN: 869506 Hom.: 0 AF XY: 0.000227 AC XY: 92 AN XY: 404822

African (AFR) AF: 0.000295 AC: 5 AN: 16958

American (AMR) AF: 0.000434 AC: 1 AN: 2304

Ashkenazi Jewish (ASJ) AF: 0.000152 AC: 1 AN: 6598

East Asian (EAS) AF: 0.00244 AC: 17 AN: 6970

South Asian (SAS) AF: 0.000285 AC: 5 AN: 17514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1850

European-Non Finnish (NFE) AF: 0.000227 AC: 178 AN: 782828

Other (OTH) AF: 0.000268 AC: 8 AN: 29858

GnomAD4 genome AF: 0.000253 AC: 36 AN: 142226 Hom.: 0 Cov.: 30 AF XY: 0.000203 AC XY: 14 AN XY: 69132

African (AFR) AF: 0.000152 AC: 6 AN: 39434

American (AMR) AF: 0.000275 AC: 4 AN: 14520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3358

East Asian (EAS) AF: 0.000414 AC: 2 AN: 4832

South Asian (SAS) AF: 0.000215 AC: 1 AN: 4650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000342 AC: 22 AN: 64308

Other (OTH) AF: 0.000512 AC: 1 AN: 1952

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

Splicing

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

Other links and lift over

dbSNP: rs1046394316; hg19: chr6-157098952;