chr6-157167191-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001374828.1(ARID1B):​c.3235+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00491 in 1,603,540 control chromosomes in the GnomAD database, including 27 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0050 ( 25 hom. )

Consequence

ARID1B
NM_001374828.1 splice_region, intron

Scores

2
Splicing: ADA: 0.00007175
2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.372
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 6-157167191-C-T is Benign according to our data. Variant chr6-157167191-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 210280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-157167191-C-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00393 (599/152314) while in subpopulation NFE AF= 0.00651 (443/68026). AF 95% confidence interval is 0.00601. There are 2 homozygotes in gnomad4. There are 283 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 599 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARID1BNM_001374828.1 linkuse as main transcriptc.3235+6C>T splice_region_variant, intron_variant ENST00000636930.2 NP_001361757.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARID1BENST00000636930.2 linkuse as main transcriptc.3235+6C>T splice_region_variant, intron_variant 2 NM_001374828.1 ENSP00000490491.2 Q8NFD5-3A0A6Q8NVI4

Frequencies

GnomAD3 genomes
AF:
0.00393
AC:
598
AN:
152196
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000989
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00425
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00290
Gnomad FIN
AF:
0.000753
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.00651
Gnomad OTH
AF:
0.00622
GnomAD3 exomes
AF:
0.00383
AC:
923
AN:
241144
Hom.:
0
AF XY:
0.00417
AC XY:
547
AN XY:
131080
show subpopulations
Gnomad AFR exome
AF:
0.000873
Gnomad AMR exome
AF:
0.00376
Gnomad ASJ exome
AF:
0.00412
Gnomad EAS exome
AF:
0.000166
Gnomad SAS exome
AF:
0.00250
Gnomad FIN exome
AF:
0.000540
Gnomad NFE exome
AF:
0.00555
Gnomad OTH exome
AF:
0.00536
GnomAD4 exome
AF:
0.00502
AC:
7278
AN:
1451226
Hom.:
25
Cov.:
30
AF XY:
0.00504
AC XY:
3641
AN XY:
722438
show subpopulations
Gnomad4 AFR exome
AF:
0.000689
Gnomad4 AMR exome
AF:
0.00396
Gnomad4 ASJ exome
AF:
0.00460
Gnomad4 EAS exome
AF:
0.0000506
Gnomad4 SAS exome
AF:
0.00263
Gnomad4 FIN exome
AF:
0.000626
Gnomad4 NFE exome
AF:
0.00570
Gnomad4 OTH exome
AF:
0.00518
GnomAD4 genome
AF:
0.00393
AC:
599
AN:
152314
Hom.:
2
Cov.:
33
AF XY:
0.00380
AC XY:
283
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.000986
Gnomad4 AMR
AF:
0.00431
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00290
Gnomad4 FIN
AF:
0.000753
Gnomad4 NFE
AF:
0.00651
Gnomad4 OTH
AF:
0.00616
Alfa
AF:
0.00578
Hom.:
0
Bravo
AF:
0.00411
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00772
EpiControl
AF:
0.00729

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:8
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 22, 2024- -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 31, 2019This variant is associated with the following publications: (PMID: 22405089) -
Likely benign, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsMay 11, 2016- -
Likely benign, no assertion criteria providedclinical testingLaboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)-- -
Likely benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenSep 01, 2024ARID1B: BP4, BS1, BS2 -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoMar 22, 2016- -
ARID1B-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMar 18, 2022This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Coffin-Siris syndrome 1 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 15, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
9.8
DANN
Benign
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000072
dbscSNV1_RF
Benign
0.0040
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148976215; hg19: chr6-157488325; COSMIC: COSV99273445; COSMIC: COSV99273445; API