rs61738955

chr6-157201226-G-Achr6-157201226-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001374828.1(ARID1B):c.5001G>A(p.Pro1667=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 1,613,808 control chromosomes in the GnomAD database, including 1,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (76 hom., cov: 32)
  • Exomes 𝑓: 0.035 (983 hom.)
• Consequence: ARID1B NM_001374828.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.81

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 6-157201226-G-A is Benign according to our data. Variant chr6-157201226-G-A is described in ClinVar as [Benign]. Clinvar id is 126334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.81 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0277 (4222/152232) while in subpopulation NFE AF= 0.0388 (2642/68010). AF 95% confidence interval is 0.0376. There are 76 homozygotes in gnomad4. There are 2005 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 4226 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.5001G>A	p.Pro1667=	synonymous_variant	18/20	ENST00000636930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.5001G>A	p.Pro1667=	synonymous_variant	18/20	2	NM_001374828.1	A2

Frequencies

GnomAD3 genomes AF: 0.0278 AC: 4226 AN: 152114 Hom.: 77 Cov.: 32

Gnomad AFR AF: 0.00746

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0355

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.0311

GnomAD3 exomes AF: 0.0277 AC: 6955 AN: 251138 Hom.: 130 AF XY: 0.0280 AC XY: 3802 AN XY: 135736

Gnomad AFR exome AF: 0.00658

Gnomad AMR exome AF: 0.0233

Gnomad ASJ exome AF: 0.0339

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0132

Gnomad FIN exome AF: 0.0372

Gnomad NFE exome AF: 0.0380

Gnomad OTH exome AF: 0.0295

GnomAD4 exome AF: 0.0355 AC: 51856 AN: 1461576 Hom.: 983 Cov.: 31 AF XY: 0.0351 AC XY: 25494 AN XY: 727038

Gnomad4 AFR exome AF: 0.00672

Gnomad4 AMR exome AF: 0.0231

Gnomad4 ASJ exome AF: 0.0345

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0136

Gnomad4 FIN exome AF: 0.0345

Gnomad4 NFE exome AF: 0.0401

Gnomad4 OTH exome AF: 0.0310

GnomAD4 genome AF: 0.0277 AC: 4222 AN: 152232 Hom.: 76 Cov.: 32 AF XY: 0.0269 AC XY: 2005 AN XY: 74436

Gnomad4 AFR AF: 0.00744

Gnomad4 AMR AF: 0.0367

Gnomad4 ASJ AF: 0.0355

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.0322

Gnomad4 NFE AF: 0.0388

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0342 Hom.: 39

Bravo AF: 0.0286

Asia WGS AF: 0.00837 AC: 29 AN: 3478

EpiCase AF: 0.0403

EpiControl AF: 0.0444

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 07, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 08, 2013

- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 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. -

Coffin-Siris syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	1.7
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs61738955; hg19: chr6-157522360; COSMIC: COSV51659391; COSMIC: COSV51659391;