6-156777698-A-AGCG

Variant names:

• chr6-156777698-A-AGCG
• rs1046451353
• NM_001374828.1:c.40_42dupGCG

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The NM_001374828.1(ARID1B):​c.40_42dupGCG​(p.Ala14dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 143,582 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID1B NM_001374828.1 conservative_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.09
• 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 -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156777698-A-AGCG is Benign according to our data. Variant chr6-156777698-A-AGCG is described in ClinVar as Likely_benign. ClinVar VariationId is 4281175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00134 (193/143582) while in subpopulation EAS AF = 0.0038 (18/4742). AF 95% confidence interval is 0.00245. There are 0 homozygotes in GnomAd4. There are 84 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 193 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.40_42dupGCG	p.Ala14dup	conservative_inframe_insertion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.40_42dupGCG	p.Ala14dup	conservative_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.40_42dupGCG	p.Ala14dup	conservative_inframe_insertion	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.40_42dupGCG	p.Ala14dup	conservative_inframe_insertion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.40_42dupGCG	p.Ala14dup	conservative_inframe_insertion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.40_42dupGCG	p.Ala14dup	conservative_inframe_insertion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.00134 AC: 193 AN: 143530 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00233

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000619

Gnomad ASJ AF: 0.00149

Gnomad EAS AF: 0.00378

Gnomad SAS AF: 0.00196

Gnomad FIN AF: 0.000493

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000814

Gnomad OTH AF: 0.00101

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00158 AC: 5 AN: 3162 Hom.: 2 Cov.: 0 AF XY: 0.00334 AC XY: 5 AN XY: 1498

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

African (AFR) AF: 0.0385 AC: 2 AN: 52

American (AMR) AF: 0.00 AC: 0 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14

East Asian (EAS) AF: 0.00 AC: 0 AN: 18

South Asian (SAS) AF: 0.00 AC: 0 AN: 214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 16

European-Non Finnish (NFE) AF: 0.00111 AC: 3 AN: 2710

Other (OTH) AF: 0.00 AC: 0 AN: 124

⚠️ 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 AF: 0.00134 AC: 193 AN: 143582 Hom.: 0 Cov.: 31 AF XY: 0.00120 AC XY: 84 AN XY: 69816

African (AFR) AF: 0.00233 AC: 93 AN: 39986

American (AMR) AF: 0.000618 AC: 9 AN: 14570

Ashkenazi Jewish (ASJ) AF: 0.00149 AC: 5 AN: 3364

East Asian (EAS) AF: 0.00380 AC: 18 AN: 4742

South Asian (SAS) AF: 0.00196 AC: 9 AN: 4582

European-Finnish (FIN) AF: 0.000493 AC: 4 AN: 8108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.000815 AC: 53 AN: 65064

Other (OTH) AF: 0.000999 AC: 2 AN: 2002

Alfa AF: 0.000111 Hom.: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs1046451353; hg19: chr6-157098832;