NM_001374828.1:c.18_20dupAGC

Variant names:

• chr6-156777692-G-GGCA
• rs557453022
• NM_001374828.1:c.18_20dupAGC

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_001374828.1(ARID1B):​c.18_20dupAGC​(p.Ala7dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0504 in 148,240 control chromosomes in the GnomAD database, including 237 homozygotes. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A7A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.050 (233 hom., cov: 30)
  • Exomes 𝑓: 0.050 (4 hom.)
• Consequence: ARID1B NM_001374828.1 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.54
• 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 6-156777692-G-GGCA is Benign according to our data. Variant chr6-156777692-G-GGCA is described in ClinVar as Benign. ClinVar VariationId is 1282345.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.075 is higher than 0.05.

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.18_20dupAGC	p.Ala7dup	disruptive_inframe_insertion	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.18_20dupAGC	p.Ala7dup	disruptive_inframe_insertion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.18_20dupAGC	p.Ala7dup	disruptive_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.18_20dupAGC	p.Ala7dup	disruptive_inframe_insertion	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.18_20dupAGC	p.Ala7dup	disruptive_inframe_insertion	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.18_20dupAGC	p.Ala7dup	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7357 AN: 145842 Hom.: 233 Cov.: 30

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.000201

Gnomad SAS AF: 0.0406

Gnomad FIN AF: 0.0514

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0767

Gnomad OTH AF: 0.0553

GnomAD4 exome AF: 0.0501 AC: 118 AN: 2356 Hom.: 4 Cov.: 0 AF XY: 0.0470 AC XY: 52 AN XY: 1106

African (AFR) AF: 0.0526 AC: 2 AN: 38

American (AMR) AF: 0.00 AC: 0 AN: 8

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.0981 AC: 21 AN: 214

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.167 AC: 2 AN: 12

European-Non Finnish (NFE) AF: 0.0460 AC: 91 AN: 1978

Other (OTH) AF: 0.0227 AC: 2 AN: 88

GnomAD4 genome AF: 0.0504 AC: 7356 AN: 145884 Hom.: 233 Cov.: 30 AF XY: 0.0493 AC XY: 3497 AN XY: 70976

African (AFR) AF: 0.0142 AC: 579 AN: 40758

American (AMR) AF: 0.0446 AC: 658 AN: 14762

Ashkenazi Jewish (ASJ) AF: 0.0704 AC: 239 AN: 3396

East Asian (EAS) AF: 0.000202 AC: 1 AN: 4954

South Asian (SAS) AF: 0.0405 AC: 193 AN: 4764

European-Finnish (FIN) AF: 0.0514 AC: 428 AN: 8322

Middle Eastern (MID) AF: 0.106 AC: 30 AN: 284

European-Non Finnish (NFE) AF: 0.0768 AC: 5045 AN: 65724

Other (OTH) AF: 0.0554 AC: 112 AN: 2020

Alfa AF: 0.0163 Hom.: 9

Asia WGS AF: 0.0200 AC: 67 AN: 3236

ClinVar

ClinVar submissions

Significance: 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		4.5

Splicing

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

Other links and lift over

dbSNP: rs557453022; hg19: chr6-157098826;