6-157184284-C-T

Variant names:

• chr6-157184284-C-T
• rs142391292
• NM_001374828.1:c.3768C>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.3768C>T​(p.Thr1256Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 1,614,130 control chromosomes in the GnomAD database, including 12 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 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (12 hom.)
• Consequence: ARID1B NM_001374828.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.222
• 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: Orphanet, Illumina, ClinGen
• Coffin-Siris syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 6-157184284-C-T is Benign according to our data. Variant chr6-157184284-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 434360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.222 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00303 (461/152300) while in subpopulation AMR AF = 0.0047 (72/15304). AF 95% confidence interval is 0.0039. There are 0 homozygotes in GnomAd4. There are 218 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 461 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	NM_001374828.1	MANE Select	c.3768C>T	p.Thr1256Thr	synonymous	Exon 13 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.3897C>T	p.Thr1299Thr	synonymous	Exon 14 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.3810C>T	p.Thr1270Thr	synonymous	Exon 14 of 21	NP_001425412.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.3768C>T	p.Thr1256Thr	synonymous	Exon 13 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.3648C>T	p.Thr1216Thr	synonymous	Exon 14 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.3609C>T	p.Thr1203Thr	synonymous	Exon 12 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.00303 AC: 461 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00431

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00290 AC: 730 AN: 251374 AF XY: 0.00295

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.00724

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00199

Gnomad NFE exome AF: 0.00442

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00419 AC: 6118 AN: 1461830 Hom.: 12 Cov.: 31 AF XY: 0.00405 AC XY: 2945 AN XY: 727208

African (AFR) AF: 0.000777 AC: 26 AN: 33480

American (AMR) AF: 0.00192 AC: 86 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00597 AC: 156 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

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

European-Finnish (FIN) AF: 0.00202 AC: 108 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00489 AC: 5433 AN: 1111966

Other (OTH) AF: 0.00409 AC: 247 AN: 60392

GnomAD4 genome AF: 0.00303 AC: 461 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.00293 AC XY: 218 AN XY: 74476

African (AFR) AF: 0.000986 AC: 41 AN: 41570

American (AMR) AF: 0.00470 AC: 72 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4826

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10608

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

European-Non Finnish (NFE) AF: 0.00431 AC: 293 AN: 68018

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00454 Hom.: 0

Bravo AF: 0.00300

EpiCase AF: 0.00485

EpiControl AF: 0.00403

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Coffin-Siris syndrome 1 (2)
-	-	1	ARID1B-related disorder (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.64
DANN	Benign	0.90
PhyloP100		-0.22
Mutation Taster		=82/18	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: rs142391292; hg19: chr6-157505418; COSMIC: COSV99266830;