NM_001374828.1:c.2247+4763C>G

Variant names:

• chr6-156940339-C-G
• rs6901717
• NM_001374828.1:c.2247+4763C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001374828.1(ARID1B):​c.2247+4763C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,084 control chromosomes in the GnomAD database, including 5,233 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (5233 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ARID1B NM_001374828.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.995
• Publications: 2 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

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.2247+4763C>G		intron	N/A	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.2247+4763C>G		intron	N/A	NP_001425411.1
	ARID1B	NM_001438483.1		c.2247+4763C>G		intron	N/A	NP_001425412.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.2247+4763C>G		intron	N/A	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.2286+4763C>G		intron	N/A	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.2247+4763C>G		intron	N/A	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32715 AN: 151964 Hom.: 5214 Cov.: 33

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.216 AC: 32780 AN: 152082 Hom.: 5233 Cov.: 33 AF XY: 0.215 AC XY: 16006 AN XY: 74322

African (AFR) AF: 0.444 AC: 18410 AN: 41468

American (AMR) AF: 0.145 AC: 2210 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3472

East Asian (EAS) AF: 0.316 AC: 1634 AN: 5174

South Asian (SAS) AF: 0.125 AC: 605 AN: 4824

European-Finnish (FIN) AF: 0.163 AC: 1726 AN: 10558

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6911 AN: 67986

Other (OTH) AF: 0.210 AC: 443 AN: 2106

Alfa AF: 0.0554 Hom.: 65

Bravo AF: 0.224

Asia WGS AF: 0.256 AC: 888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		0.99
Mutation Taster		=100/0	polymorphism (auto)

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: rs6901717; hg19: chr6-157261473;