NM_001374828.1:c.318G>A

Variant names:

• chr6-156777998-G-A
• rs533182720
• NM_001374828.1:c.318G>A

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.318G>A​(p.Ala106Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00041 in 1,531,480 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A106A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: ARID1B NM_001374828.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.146
• 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: Illumina, ClinGen, Orphanet
• Coffin-Siris syndrome 1

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

ENSG00000271551 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 6-156777998-G-A is Benign according to our data. Variant chr6-156777998-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 126337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.146 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00242 (365/151064) while in subpopulation AFR AF = 0.00797 (329/41290). AF 95% confidence interval is 0.00726. There are 2 homozygotes in GnomAd4. There are 189 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 365 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.318G>A	p.Ala106Ala	synonymous	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.318G>A	p.Ala106Ala	synonymous	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.318G>A	p.Ala106Ala	synonymous	Exon 1 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.318G>A	p.Ala106Ala	synonymous	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.318G>A	p.Ala106Ala	synonymous	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.318G>A	p.Ala106Ala	synonymous	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.00242 AC: 365 AN: 150950 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00799

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00197

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: 0.0000297

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.000587 AC: 75 AN: 127740 AF XY: 0.000514

Gnomad AFR exome AF: 0.00813

Gnomad AMR exome AF: 0.000788

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000638

Gnomad OTH exome AF: 0.000759

GnomAD4 exome AF: 0.000191 AC: 263 AN: 1380416 Hom.: 0 Cov.: 34 AF XY: 0.000159 AC XY: 108 AN XY: 680946

African (AFR) AF: 0.00589 AC: 185 AN: 31406

American (AMR) AF: 0.000932 AC: 33 AN: 35412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25064

East Asian (EAS) AF: 0.00 AC: 0 AN: 35604

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34264

Middle Eastern (MID) AF: 0.000637 AC: 3 AN: 4708

European-Non Finnish (NFE) AF: 0.00000557 AC: 6 AN: 1077380

Other (OTH) AF: 0.000607 AC: 35 AN: 57648

GnomAD4 genome AF: 0.00242 AC: 365 AN: 151064 Hom.: 2 Cov.: 31 AF XY: 0.00256 AC XY: 189 AN XY: 73788

African (AFR) AF: 0.00797 AC: 329 AN: 41290

American (AMR) AF: 0.00197 AC: 30 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5042

South Asian (SAS) AF: 0.00 AC: 0 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000297 AC: 2 AN: 67432

Other (OTH) AF: 0.00190 AC: 4 AN: 2104

Alfa AF: 0.000428 Hom.: 0

Bravo AF: 0.00291

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	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	-0.70
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		0.15
PromoterAI		-0.049	Neutral
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: rs533182720; hg19: chr6-157099132;