rs771557031

chr6-156778915-CAGGAGCAGG-Cchr6-156778915-CAGGAGCAGG-CAGGAGCAGGAGGAGCAGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3 BP6 BS1 BS2

The NM_001374828.1(ARID1B):c.1247_1255del(p.Gly416_Gly418del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,322,332 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: ARID1B NM_001374828.1 inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: 1.36

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 -10 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156778915-CAGGAGCAGG-C is Benign according to our data. Variant chr6-156778915-CAGGAGCAGG-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210315.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=4, Benign=1}.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000392 (55/140424) while in subpopulation AFR AF= 0.000866 (33/38098). AF 95% confidence interval is 0.000633. There are 0 homozygotes in gnomad4. There are 29 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.1247_1255del	p.Gly416_Gly418del	inframe_deletion	1/20	ENST00000636930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.1247_1255del	p.Gly416_Gly418del	inframe_deletion	1/20	2	NM_001374828.1	A2

Frequencies

GnomAD3 genomes AF: 0.000392 AC: 55 AN: 140340 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000490

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000536 AC: 1 AN: 18646 Hom.: 0 AF XY: 0.0000889 AC XY: 1 AN XY: 11244

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000297

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000228 AC: 269 AN: 1181908 Hom.: 0 AF XY: 0.000240 AC XY: 138 AN XY: 575624

Gnomad4 AFR exome AF: 0.000683

Gnomad4 AMR exome AF: 0.000481

Gnomad4 ASJ exome AF: 0.0000598

Gnomad4 EAS exome AF: 0.000165

Gnomad4 SAS exome AF: 0.000325

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000227

Gnomad4 OTH exome AF: 0.000146

GnomAD4 genome AF: 0.000392 AC: 55 AN: 140424 Hom.: 0 Cov.: 29 AF XY: 0.000422 AC XY: 29 AN XY: 68642

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.000489

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:5

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Nov 24, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2020	- -

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 12, 2015

- -

ARID1B-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 19, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 08, 2018

This alteration is classified as likely 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

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

Publications

LitVar

Other links and lift over

dbSNP: rs771557031; hg19: chr6-157100049;