rs587779748

Positions:

• chr6-156778871-CGGA-C
• chr6-156778871-CGGA-CGGAGGA
• chr6-156778871-CGGA-CGGAGGAGGA

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The NM_001374828.1(ARID1B):​c.1203_1205del​(p.Gly402del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,339,750 control chromosomes in the GnomAD database, including 89 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G398G) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0092 (11 hom., cov: 29)
  • Exomes 𝑓: 0.012 (78 hom.)
• Consequence: ARID1B NM_001374828.1 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 2.06

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778871-CGGA-C is Benign according to our data. Variant chr6-156778871-CGGA-C is described in ClinVar as [Likely_benign]. Clinvar id is 126340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-156778871-CGGA-C is described in Lovd as [Likely_benign]. Variant chr6-156778871-CGGA-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0092 (1351/146914) while in subpopulation SAS AF= 0.0151 (70/4650). AF 95% confidence interval is 0.0122. There are 11 homozygotes in gnomad4. There are 654 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1351 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.1203_1205del	p.Gly402del	inframe_deletion	1/20	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.1203_1205del	p.Gly402del	inframe_deletion	1/20	2	NM_001374828.1	ENSP00000490491	A2

Frequencies

GnomAD3 genomes AF: 0.00921 AC: 1352 AN: 146820 Hom.: 11 Cov.: 29

Gnomad AFR AF: 0.00180

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0430

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0150

Gnomad FIN AF: 0.00506

Gnomad MID AF: 0.0142

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.00846

GnomAD3 exomes AF: 0.0119 AC: 513 AN: 43244 Hom.: 7 AF XY: 0.0130 AC XY: 330 AN XY: 25448

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00946

Gnomad ASJ exome AF: 0.0409

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0138

Gnomad FIN exome AF: 0.00487

Gnomad NFE exome AF: 0.0111

Gnomad OTH exome AF: 0.0108

GnomAD4 exome AF: 0.0116 AC: 13853 AN: 1192836 Hom.: 78 AF XY: 0.0119 AC XY: 6930 AN XY: 583416

Gnomad4 AFR exome AF: 0.00149

Gnomad4 AMR exome AF: 0.00860

Gnomad4 ASJ exome AF: 0.0432

Gnomad4 EAS exome AF: 0.0000375

Gnomad4 SAS exome AF: 0.0136

Gnomad4 FIN exome AF: 0.00610

Gnomad4 NFE exome AF: 0.0117

Gnomad4 OTH exome AF: 0.0131

GnomAD4 genome AF: 0.00920 AC: 1351 AN: 146914 Hom.: 11 Cov.: 29 AF XY: 0.00912 AC XY: 654 AN XY: 71748

Gnomad4 AFR AF: 0.00180

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.0430

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.00506

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.00839

Alfa AF: 0.00861 Hom.: 8

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:5

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 06, 2020	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	ARID1B: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	Nov 03, 2021	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	May 27, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs587779748; hg19: chr6-157100005;