NM_001374828.1:c.40_42delGCG

Variant names:

• chr6-156777698-AGCG-A
• rs1046451353
• NM_001374828.1:c.40_42delGCG

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_001374828.1(ARID1B):​c.40_42delGCG​(p.Ala14del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 143,530 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0038 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID1B NM_001374828.1 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.16
• 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: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BS2: High AC in GnomAd4 at 21 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_42delGCG	p.Ala14del	conservative_inframe_deletion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.40_42delGCG	p.Ala14del	conservative_inframe_deletion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.40_42delGCG	p.Ala14del	conservative_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.40_42delGCG	p.Ala14del	conservative_inframe_deletion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.40_42delGCG	p.Ala14del	conservative_inframe_deletion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.40_42delGCG	p.Ala14del	conservative_inframe_deletion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.000146 AC: 21 AN: 143530 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000210

Gnomad SAS AF: 0.000436

Gnomad FIN AF: 0.000123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000169

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00382 AC: 12 AN: 3140 Hom.: 0 AF XY: 0.00672 AC XY: 10 AN XY: 1488

⚠️ 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: 52

American (AMR) AF: 0.0833 AC: 1 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12

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

South Asian (SAS) AF: 0.00476 AC: 1 AN: 210

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: 0.00334 AC: 9 AN: 2694

Other (OTH) AF: 0.00806 AC: 1 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: 0.000146 AC: 21 AN: 143530 Hom.: 0 Cov.: 31 AF XY: 0.000201 AC XY: 14 AN XY: 69754

African (AFR) AF: 0.000100 AC: 4 AN: 39918

American (AMR) AF: 0.000137 AC: 2 AN: 14550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3364

East Asian (EAS) AF: 0.000210 AC: 1 AN: 4762

South Asian (SAS) AF: 0.000436 AC: 2 AN: 4588

European-Finnish (FIN) AF: 0.000123 AC: 1 AN: 8108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000169 AC: 11 AN: 65072

Other (OTH) AF: 0.00 AC: 0 AN: 1984

Alfa AF: 0.00 Hom.: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Coffin-Siris syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

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;