rs533517668

Variant names:

• chr6-156778643-C-T
• rs533517668
• NM_001374828.1:c.963C>T

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.963C>T​(p.Ala321Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,473,968 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0018 (2 hom.)
• Consequence: ARID1B NM_001374828.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.157
• Publications: 0 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

ENSG00000296922 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 6-156778643-C-T is Benign according to our data. Variant chr6-156778643-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 434352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.157 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00102 (152/148516) while in subpopulation NFE AF = 0.00192 (128/66808). AF 95% confidence interval is 0.00165. There are 0 homozygotes in GnomAd4. There are 68 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 152 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.963C>T	p.Ala321Ala	synonymous	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.963C>T	p.Ala321Ala	synonymous	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.963C>T	p.Ala321Ala	synonymous	Exon 1 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.963C>T	p.Ala321Ala	synonymous	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.963C>T	p.Ala321Ala	synonymous	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.963C>T	p.Ala321Ala	synonymous	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.00102 AC: 152 AN: 148418 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000395

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00192

Gnomad OTH AF: 0.000981

GnomAD2 exomes AF: 0.00112 AC: 107 AN: 95338 AF XY: 0.00116

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00166

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00181

Gnomad OTH exome AF: 0.00331

GnomAD4 exome AF: 0.00176 AC: 2335 AN: 1325452 Hom.: 2 Cov.: 37 AF XY: 0.00173 AC XY: 1134 AN XY: 653670

African (AFR) AF: 0.000146 AC: 4 AN: 27386

American (AMR) AF: 0.00160 AC: 48 AN: 30064

Ashkenazi Jewish (ASJ) AF: 0.0000429 AC: 1 AN: 23296

East Asian (EAS) AF: 0.0000680 AC: 2 AN: 29418

South Asian (SAS) AF: 0.000414 AC: 30 AN: 72522

European-Finnish (FIN) AF: 0.0000953 AC: 4 AN: 41994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4846

European-Non Finnish (NFE) AF: 0.00210 AC: 2184 AN: 1041788

Other (OTH) AF: 0.00115 AC: 62 AN: 54138

GnomAD4 genome AF: 0.00102 AC: 152 AN: 148516 Hom.: 0 Cov.: 30 AF XY: 0.000937 AC XY: 68 AN XY: 72576

African (AFR) AF: 0.000394 AC: 16 AN: 40584

American (AMR) AF: 0.000398 AC: 6 AN: 15060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 4858

South Asian (SAS) AF: 0.00 AC: 0 AN: 4722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.00192 AC: 128 AN: 66808

Other (OTH) AF: 0.000973 AC: 2 AN: 2056

Alfa AF: 0.00129 Hom.: 0

Bravo AF: 0.00125

ClinVar

ClinVar submissions as Germline

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	-0.56
CADD	Benign	15
DANN	Uncertain	0.98
PhyloP100		-0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=98/2	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: rs533517668; hg19: chr6-157099777; COSMIC: COSV104368484;