6-156935516-C-T

Variant names:

• chr6-156935516-C-T
• rs146240413
• NM_001374828.1:c.2187C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001374828.1(ARID1B):​c.2187C>T​(p.Pro729Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00431 in 1,613,896 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0044 (20 hom.)
• Consequence: ARID1B NM_001374828.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.914
• Publications: 4 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 6-156935516-C-T is Benign according to our data. Variant chr6-156935516-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.914 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00298 (454/152202) while in subpopulation NFE AF = 0.00488 (332/68010). AF 95% confidence interval is 0.00445. There are 1 homozygotes in GnomAd4. There are 216 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 454 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.2187C>T	p.Pro729Pro	synonymous	Exon 4 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.2187C>T	p.Pro729Pro	synonymous	Exon 4 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.2187C>T	p.Pro729Pro	synonymous	Exon 4 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.2187C>T	p.Pro729Pro	synonymous	Exon 4 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.2226C>T	p.Pro742Pro	synonymous	Exon 6 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.2187C>T	p.Pro729Pro	synonymous	Exon 4 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.00299 AC: 454 AN: 152084 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00488

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00251 AC: 630 AN: 251438 AF XY: 0.00247

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.00410

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00444 AC: 6494 AN: 1461694 Hom.: 20 Cov.: 30 AF XY: 0.00422 AC XY: 3065 AN XY: 727162

African (AFR) AF: 0.000717 AC: 24 AN: 33478

American (AMR) AF: 0.00239 AC: 107 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000696 AC: 60 AN: 86252

European-Finnish (FIN) AF: 0.00133 AC: 71 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00535 AC: 5950 AN: 1111872

Other (OTH) AF: 0.00467 AC: 282 AN: 60378

GnomAD4 genome AF: 0.00298 AC: 454 AN: 152202 Hom.: 1 Cov.: 31 AF XY: 0.00290 AC XY: 216 AN XY: 74412

African (AFR) AF: 0.00106 AC: 44 AN: 41518

American (AMR) AF: 0.00308 AC: 47 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4826

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00488 AC: 332 AN: 68010

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00305 Hom.: 1

Bravo AF: 0.00290

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00447

EpiControl AF: 0.00302

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	ARID1B-related disorder (1)
-	-	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	-0.30
CADD	Benign	9.1
DANN	Benign	0.63
PhyloP100		-0.91
PromoterAI		-0.0048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs146240413; hg19: chr6-157256650; COSMIC: COSV51677368;