rs3734441

Variant names:

• chr6-157084796-G-A
• rs3734441
• NM_001374828.1:c.2382G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-157084796-G-A
• chr6-157084796-G-C
• chr6-157084796-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001374828.1(ARID1B):​c.2382G>A​(p.Ala794Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,613,790 control chromosomes in the GnomAD database, including 219,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17741 hom., cov: 31)
  • Exomes 𝑓: 0.52 (202040 hom.)
• Consequence: ARID1B NM_001374828.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.618
• Publications: 23 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)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-157084796-G-A is Benign according to our data. Variant chr6-157084796-G-A is described in ClinVar as Benign. ClinVar VariationId is 126320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.618 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.566 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.2382G>A	p.Ala794Ala	synonymous	Exon 5 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.2382G>A	p.Ala794Ala	synonymous	Exon 5 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.2424G>A	p.Ala808Ala	synonymous	Exon 6 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.2382G>A	p.Ala794Ala	synonymous	Exon 5 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.2421G>A	p.Ala807Ala	synonymous	Exon 7 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.2382G>A	p.Ala794Ala	synonymous	Exon 5 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71824 AN: 151786 Hom.: 17738 Cov.: 31

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.499

GnomAD2 exomes AF: 0.523 AC: 131459 AN: 251256 AF XY: 0.527

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.610

Gnomad ASJ exome AF: 0.608

Gnomad EAS exome AF: 0.550

Gnomad FIN exome AF: 0.389

Gnomad NFE exome AF: 0.527

Gnomad OTH exome AF: 0.521

GnomAD4 exome AF: 0.523 AC: 764659 AN: 1461886 Hom.: 202040 Cov.: 80 AF XY: 0.525 AC XY: 381655 AN XY: 727244

African (AFR) AF: 0.333 AC: 11165 AN: 33480

American (AMR) AF: 0.603 AC: 26986 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 15845 AN: 26136

East Asian (EAS) AF: 0.571 AC: 22668 AN: 39698

South Asian (SAS) AF: 0.571 AC: 49228 AN: 86258

European-Finnish (FIN) AF: 0.392 AC: 20942 AN: 53420

Middle Eastern (MID) AF: 0.549 AC: 3168 AN: 5768

European-Non Finnish (NFE) AF: 0.524 AC: 583242 AN: 1112006

Other (OTH) AF: 0.520 AC: 31415 AN: 60396

GnomAD4 genome AF: 0.473 AC: 71858 AN: 151904 Hom.: 17741 Cov.: 31 AF XY: 0.472 AC XY: 35011 AN XY: 74246

African (AFR) AF: 0.340 AC: 14086 AN: 41420

American (AMR) AF: 0.558 AC: 8533 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2045 AN: 3472

East Asian (EAS) AF: 0.553 AC: 2844 AN: 5144

South Asian (SAS) AF: 0.584 AC: 2802 AN: 4794

European-Finnish (FIN) AF: 0.386 AC: 4074 AN: 10550

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.524 AC: 35625 AN: 67924

Other (OTH) AF: 0.499 AC: 1051 AN: 2108

Alfa AF: 0.517 Hom.: 82707

Bravo AF: 0.479

Asia WGS AF: 0.526 AC: 1831 AN: 3478

EpiCase AF: 0.539

EpiControl AF: 0.541

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Coffin-Siris syndrome 1 (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.60
DANN	Benign	0.62
PhyloP100		-0.62
PromoterAI		-0.012	Neutral
Mutation Taster		=76/24	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3734441; hg19: chr6-157405930; COSMIC: COSV51659621;