NM_001374828.1:c.4383-7A>G

Variant names:

• chr6-157198804-A-G
• rs112318565
• NM_001374828.1:c.4383-7A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001374828.1(ARID1B):​c.4383-7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0587 in 1,604,956 control chromosomes in the GnomAD database, including 7,292 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (3167 hom., cov: 33)
  • Exomes 𝑓: 0.051 (4125 hom.)
• Consequence: ARID1B NM_001374828.1 splice_region, intron
• Scores: Splicing: ADA: 0.00002729
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.414
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-157198804-A-G is Benign according to our data. Variant chr6-157198804-A-G is described in ClinVar as Benign. ClinVar VariationId is 126330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.4383-7A>G		splice_region_variant, intron_variant	Intron 16 of 19	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.4383-7A>G		splice_region_variant, intron_variant	Intron 16 of 19	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20378 AN: 152094 Hom.: 3141 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.0495

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0286

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0391

Gnomad OTH AF: 0.120

GnomAD2 exomes AF: 0.0564 AC: 13700 AN: 242846 AF XY: 0.0476

Gnomad AFR exome AF: 0.386

Gnomad AMR exome AF: 0.0553

Gnomad ASJ exome AF: 0.0401

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.0308

Gnomad NFE exome AF: 0.0392

Gnomad OTH exome AF: 0.0423

GnomAD4 exome AF: 0.0507 AC: 73703 AN: 1452744 Hom.: 4125 Cov.: 30 AF XY: 0.0479 AC XY: 34612 AN XY: 721842

African (AFR) AF: 0.392 AC: 13042 AN: 33300

American (AMR) AF: 0.0580 AC: 2542 AN: 43830

Ashkenazi Jewish (ASJ) AF: 0.0431 AC: 1116 AN: 25876

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39546

South Asian (SAS) AF: 0.0125 AC: 1060 AN: 84932

European-Finnish (FIN) AF: 0.0299 AC: 1587 AN: 53110

Middle Eastern (MID) AF: 0.0225 AC: 129 AN: 5740

European-Non Finnish (NFE) AF: 0.0456 AC: 50501 AN: 1106400

Other (OTH) AF: 0.0620 AC: 3721 AN: 60010

GnomAD4 genome AF: 0.134 AC: 20457 AN: 152212 Hom.: 3167 Cov.: 33 AF XY: 0.130 AC XY: 9714 AN XY: 74440

African (AFR) AF: 0.381 AC: 15783 AN: 41474

American (AMR) AF: 0.0778 AC: 1190 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0495 AC: 172 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4828

European-Finnish (FIN) AF: 0.0286 AC: 304 AN: 10620

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0392 AC: 2663 AN: 68016

Other (OTH) AF: 0.120 AC: 254 AN: 2112

Alfa AF: 0.0855 Hom.: 673

Bravo AF: 0.149

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Coffin-Siris syndrome 1 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.90
DANN	Benign	0.62
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000027
dbscSNV1_RF	Benign	0.0
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: rs112318565; hg19: chr6-157519938; COSMIC: COSV51649837;