rs61738955

Variant names:

• chr6-157201226-G-A
• rs61738955
• NM_001374828.1:c.5001G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-157201226-G-A
• chr6-157201226-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001374828.1(ARID1B):​c.5001G>A​(p.Pro1667Pro) 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
• Publications: 11 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=-0.48).
• BP6: Variant 6-157201226-G-A is Benign according to our data. Variant chr6-157201226-G-A is described in ClinVar as Benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4222 AD gene.

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.5001G>A	p.Pro1667Pro	synonymous	Exon 18 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.5130G>A	p.Pro1710Pro	synonymous	Exon 19 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.5043G>A	p.Pro1681Pro	synonymous	Exon 19 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.5001G>A	p.Pro1667Pro	synonymous	Exon 18 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.4881G>A	p.Pro1627Pro	synonymous	Exon 19 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.4842G>A	p.Pro1614Pro	synonymous	Exon 17 of 19	ENSP00000055163.8	Q8NFD5-5

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

GnomAD2 exomes AF: 0.0277 AC: 6955 AN: 251138 AF XY: 0.0280

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 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

African (AFR) AF: 0.00672 AC: 225 AN: 33480

American (AMR) AF: 0.0231 AC: 1034 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0345 AC: 902 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0136 AC: 1172 AN: 86246

European-Finnish (FIN) AF: 0.0345 AC: 1841 AN: 53306

Middle Eastern (MID) AF: 0.0335 AC: 193 AN: 5766

European-Non Finnish (NFE) AF: 0.0401 AC: 44619 AN: 1111852

Other (OTH) AF: 0.0310 AC: 1869 AN: 60378

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

African (AFR) AF: 0.00744 AC: 309 AN: 41542

American (AMR) AF: 0.0367 AC: 561 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0355 AC: 123 AN: 3468

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5164

South Asian (SAS) AF: 0.0122 AC: 59 AN: 4828

European-Finnish (FIN) AF: 0.0322 AC: 341 AN: 10602

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0388 AC: 2642 AN: 68010

Other (OTH) AF: 0.0308 AC: 65 AN: 2112

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.7
DANN	Benign	0.77
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	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: rs61738955; hg19: chr6-157522360; COSMIC: COSV51659391; COSMIC: COSV51659391;