rs12197388

chr6-157083329-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001374828.1(ARID1B):c.2248-1333T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,240 control chromosomes in the GnomAD database, including 2,107 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 0.15 (2107 hom., cov: 32)
• Consequence: ARID1B NM_001374828.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.2248-1333T>C		intron_variant		ENST00000636930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.2248-1333T>C		intron_variant		2	NM_001374828.1	A2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22222 AN: 152122 Hom.: 2106 Cov.: 32

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.00865

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.149

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.146 AC: 22226 AN: 152240 Hom.: 2107 Cov.: 32 AF XY: 0.145 AC XY: 10778 AN XY: 74434

Gnomad4 AFR AF: 0.0403

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.00886

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.147

Alfa AF: 0.190 Hom.: 2035

Bravo AF: 0.137

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.45
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs12197388; hg19: chr6-157404463;