6-156777818-C-CGCG

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The NM_001374828.1(ARID1B):c.156_158dup(p.Ala52dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,011,732 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 30)
  • Exomes 𝑓: 0.0013 (1 hom.)
• Consequence: ARID1B NM_001374828.1 inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.490

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BP6: Variant 6-156777818-C-CGCG is Benign according to our data. Variant chr6-156777818-C-CGCG is described in ClinVar as [Likely_benign]. Clinvar id is 2579011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00186 (264/142248) while in subpopulation AFR AF= 0.00278 (110/39498). AF 95% confidence interval is 0.00236. There are 1 homozygotes in gnomad4. There are 125 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd at 263 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.156_158dup	p.Ala52dup	inframe_insertion	1/20	ENST00000636930.2
LOC115308161	NR_163974.1	n.274-388_274-387insCGC		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.156_158dup	p.Ala52dup	inframe_insertion	1/20	2	NM_001374828.1	A2
	ENST00000603191.2	n.178-388_178-387insCGC		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00185 AC: 263 AN: 142230 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00276

Gnomad AMI AF: 0.00917

Gnomad AMR AF: 0.00110

Gnomad ASJ AF: 0.000298

Gnomad EAS AF: 0.00166

Gnomad SAS AF: 0.00258

Gnomad FIN AF: 0.000375

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.00154

GnomAD4 exome AF: 0.00131 AC: 1140 AN: 869484 Hom.: 1 Cov.: 18 AF XY: 0.00129 AC XY: 522 AN XY: 404808

Gnomad4 AFR exome AF: 0.00177

Gnomad4 AMR exome AF: 0.000869

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00100

Gnomad4 SAS exome AF: 0.00285

Gnomad4 FIN exome AF: 0.000216

Gnomad4 NFE exome AF: 0.00130

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.00186 AC: 264 AN: 142248 Hom.: 1 Cov.: 30 AF XY: 0.00181 AC XY: 125 AN XY: 69172

Gnomad4 AFR AF: 0.00278

Gnomad4 AMR AF: 0.00110

Gnomad4 ASJ AF: 0.000298

Gnomad4 EAS AF: 0.00166

Gnomad4 SAS AF: 0.00259

Gnomad4 FIN AF: 0.000375

Gnomad4 NFE AF: 0.00160

Gnomad4 OTH AF: 0.00152

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

ARID1B: BS1 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1046394316; hg19: chr6-157098952;