rs78253128

chr6-156778292-A-G

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.612A>G(p.Gln204=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,517,812 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. QQ204Q?) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0048 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0043 (6 hom.)
• Consequence: ARID1B NM_001374828.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.113

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-156778292-A-G is Benign according to our data. Variant chr6-156778292-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 126328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.113 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00482 (701/145396) while in subpopulation AFR AF= 0.00571 (208/36448). AF 95% confidence interval is 0.00507. There are 1 homozygotes in gnomad4. There are 353 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 701 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.612A>G	p.Gln204=	synonymous_variant	1/20	ENST00000636930.2
LOC115308161	NR_163974.1	n.227T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.612A>G	p.Gln204=	synonymous_variant	1/20	2	NM_001374828.1	A2
	ENST00000603191.2	n.131T>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.00482 AC: 701 AN: 145296 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00572

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00508

Gnomad ASJ AF: 0.00117

Gnomad EAS AF: 0.000605

Gnomad SAS AF: 0.000419

Gnomad FIN AF: 0.00737

Gnomad MID AF: 0.00327

Gnomad NFE AF: 0.00484

Gnomad OTH AF: 0.00250

GnomAD3 exomes AF: 0.00422 AC: 533 AN: 126374 Hom.: 2 AF XY: 0.00401 AC XY: 272 AN XY: 67906

Gnomad AFR exome AF: 0.00552

Gnomad AMR exome AF: 0.00320

Gnomad ASJ exome AF: 0.00143

Gnomad EAS exome AF: 0.000531

Gnomad SAS exome AF: 0.000576

Gnomad FIN exome AF: 0.0105

Gnomad NFE exome AF: 0.00582

Gnomad OTH exome AF: 0.00745

GnomAD4 exome AF: 0.00426 AC: 5851 AN: 1372416 Hom.: 6 Cov.: 37 AF XY: 0.00410 AC XY: 2779 AN XY: 677496

Gnomad4 AFR exome AF: 0.00537

Gnomad4 AMR exome AF: 0.00382

Gnomad4 ASJ exome AF: 0.00157

Gnomad4 EAS exome AF: 0.000892

Gnomad4 SAS exome AF: 0.000726

Gnomad4 FIN exome AF: 0.0100

Gnomad4 NFE exome AF: 0.00446

Gnomad4 OTH exome AF: 0.00430

GnomAD4 genome AF: 0.00482 AC: 701 AN: 145396 Hom.: 1 Cov.: 31 AF XY: 0.00496 AC XY: 353 AN XY: 71142

Gnomad4 AFR AF: 0.00571

Gnomad4 AMR AF: 0.00507

Gnomad4 ASJ AF: 0.00117

Gnomad4 EAS AF: 0.000607

Gnomad4 SAS AF: 0.000419

Gnomad4 FIN AF: 0.00737

Gnomad4 NFE AF: 0.00484

Gnomad4 OTH AF: 0.00248

Alfa AF: 0.00780 Hom.: 0

ClinVar

Significance: Benign/Likely 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	GeneDx	Sep 04, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 17, 2014

- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 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	-0.82
Cadd	Benign	4.5
Dann	Benign	0.80
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: rs78253128; hg19: chr6-157099426; COSMIC: COSV51649851; COSMIC: COSV51649851;