6-156777698-AGCG-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3 BS2

The NM_001374828.1(ARID1B):c.40_42del(p.Ala14del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 143,530 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A7A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0038 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID1B NM_001374828.1 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.16

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 Likely_benign. Variant got -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BS2: High AC in GnomAd at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.40_42del	p.Ala14del	inframe_deletion	1/20	ENST00000636930.2
LOC115308161	NR_163974.1	n.274-270_274-268del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.40_42del	p.Ala14del	inframe_deletion	1/20	2	NM_001374828.1	A2
	ENST00000603191.2	n.178-270_178-268del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.000146 AC: 21 AN: 143530 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000210

Gnomad SAS AF: 0.000436

Gnomad FIN AF: 0.000123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000169

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00382 AC: 12 AN: 3140 Hom.: 0 AF XY: 0.00672 AC XY: 10 AN XY: 1488

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0833

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00476

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00334

Gnomad4 OTH exome AF: 0.00806

GnomAD4 genome AF: 0.000146 AC: 21 AN: 143530 Hom.: 0 Cov.: 31 AF XY: 0.000201 AC XY: 14 AN XY: 69754

Gnomad4 AFR AF: 0.000100

Gnomad4 AMR AF: 0.000137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000210

Gnomad4 SAS AF: 0.000436

Gnomad4 FIN AF: 0.000123

Gnomad4 NFE AF: 0.000169

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Coffin-Siris syndrome 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Institute of Human Genetics, University Hospital of Duesseldorf

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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;