6-156777818-C-CGCGGCG

Position:

• chr6-156777818-C-CGCGGCG

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP3 BS2_Supporting

The NM_001374828.1(ARID1B):​c.153_158dup​(p.Ala52_Ala53dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 1,011,750 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000056 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: ARID1B NM_001374828.1 inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U: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 Likely_benign. Variant got -2 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BS2: High AC in GnomAd4 at 8 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.153_158dup	p.Ala52_Ala53dup	inframe_insertion	1/20	ENST00000636930.2	NP_001361757.1
LOC115308161	NR_163974.1	n.274-388_274-387insCGCCGC		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.153_158dup	p.Ala52_Ala53dup	inframe_insertion	1/20	2	NM_001374828.1	ENSP00000490491	A2
	ENST00000603191.2	n.178-388_178-387insCGCCGC		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0000562 AC: 8 AN: 142230 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000933

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000621 AC: 54 AN: 869502 Hom.: 0 Cov.: 18 AF XY: 0.0000667 AC XY: 27 AN XY: 404820

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000434

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: 0.0000664

Gnomad4 OTH exome AF: 0.0000335

GnomAD4 genome AF: 0.0000562 AC: 8 AN: 142248 Hom.: 0 Cov.: 30 AF XY: 0.0000723 AC XY: 5 AN XY: 69172

Gnomad4 AFR AF: 0.0000506

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000933

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

- -

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;