6-156777698-AGCGGCGGCG-A

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.34_42del(p.Ala12_Ala14del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 146,744 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A7A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (0 hom.)
• Consequence: ARID1B NM_001374828.1 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.54

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 6-156777698-AGCGGCGGCG-A is Benign according to our data. Variant chr6-156777698-AGCGGCGGCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 2673087.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00249 (357/143582) while in subpopulation NFE AF= 0.00289 (188/65064). AF 95% confidence interval is 0.00255. There are 0 homozygotes in gnomad4. There are 182 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 358 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.34_42del	p.Ala12_Ala14del	inframe_deletion	1/20	ENST00000636930.2
LOC115308161	NR_163974.1	n.274-276_274-268del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.34_42del	p.Ala12_Ala14del	inframe_deletion	1/20	2	NM_001374828.1	A2
	ENST00000603191.2	n.178-276_178-268del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00249 AC: 358 AN: 143530 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00186

Gnomad ASJ AF: 0.0140

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.00196

Gnomad FIN AF: 0.00333

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00289

Gnomad OTH AF: 0.00101

GnomAD4 exome AF: 0.00253 AC: 8 AN: 3162 Hom.: 0 AF XY: 0.00134 AC XY: 2 AN XY: 1498

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00258

Gnomad4 OTH exome AF: 0.00806

GnomAD4 genome AF: 0.00249 AC: 357 AN: 143582 Hom.: 0 Cov.: 31 AF XY: 0.00261 AC XY: 182 AN XY: 69816

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.00185

Gnomad4 ASJ AF: 0.0140

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.00196

Gnomad4 FIN AF: 0.00333

Gnomad4 NFE AF: 0.00289

Gnomad4 OTH AF: 0.000999

Bravo AF: 0.00243

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

Feb 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: rs1046451353; hg19: chr6-157098832;