chr6-156778607-C-A

Variant names:

• chr6-156778607-C-A
• rs1450163641
• NM_001374828.1:c.927C>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001374828.1(ARID1B):​c.927C>A​(p.Ala309Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000613 in 1,305,228 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A309A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: ARID1B NM_001374828.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.258
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 6-156778607-C-A is Benign according to our data. Variant chr6-156778607-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2725866.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.258 with no splicing effect.

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.927C>A	p.Ala309Ala	synonymous	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.927C>A	p.Ala309Ala	synonymous	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.927C>A	p.Ala309Ala	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.927C>A	p.Ala309Ala	synonymous	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.927C>A	p.Ala309Ala	synonymous	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.927C>A	p.Ala309Ala	synonymous	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.0000271 AC: 4 AN: 147454 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000992

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000345 AC: 4 AN: 1157774 Hom.: 0 Cov.: 36 AF XY: 0.00000356 AC XY: 2 AN XY: 561984

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000130 AC: 3 AN: 23158

American (AMR) AF: 0.00 AC: 0 AN: 10548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17968

East Asian (EAS) AF: 0.00 AC: 0 AN: 26680

South Asian (SAS) AF: 0.00 AC: 0 AN: 39862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3396

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 961816

Other (OTH) AF: 0.0000217 AC: 1 AN: 45992

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000768718), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000271 AC: 4 AN: 147454 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 71912

African (AFR) AF: 0.0000992 AC: 4 AN: 40324

American (AMR) AF: 0.00 AC: 0 AN: 14958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 4848

South Asian (SAS) AF: 0.00 AC: 0 AN: 4688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66436

Other (OTH) AF: 0.00 AC: 0 AN: 2046

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		-0.26

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: rs1450163641; hg19: chr6-157099741;