6-156777698-AGCGGCGGCGGCGGCG-AGCGGCGGCG

Variant names:

• chr6-156777698-AGCGGCG-A
• rs1046451353
• NM_001374828.1:c.37_42delGCGGCG

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The NM_001374828.1(ARID1B):​c.37_42delGCGGCG​(p.Ala13_Ala14del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 146,742 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (1 hom.)
• Consequence: ARID1B NM_001374828.1 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19

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]

ENSG00000271551 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001374828.1
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00152 (218/143580) while in subpopulation NFE AF= 0.00128 (83/65064). AF 95% confidence interval is 0.00105. There are 0 homozygotes in gnomad4. There are 147 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 218 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.37_42delGCGGCG	p.Ala13_Ala14del	conservative_inframe_deletion	Exon 1 of 20	ENST00000636930.2	NP_001361757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID1B	ENST00000636930.2	c.37_42delGCGGCG	p.Ala13_Ala14del	conservative_inframe_deletion	Exon 1 of 20	2	NM_001374828.1	ENSP00000490491.2

Frequencies

GnomAD3 genomes AF: 0.00152 AC: 218 AN: 143528 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000401

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000687

Gnomad ASJ AF: 0.000297

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000654

Gnomad FIN AF: 0.0128

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00128

Gnomad OTH AF: 0.000504

GnomAD4 exome AF: 0.00190 AC: 6 AN: 3162 Hom.: 1 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: 0.00221

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00152 AC: 218 AN: 143580 Hom.: 0 Cov.: 31 AF XY: 0.00211 AC XY: 147 AN XY: 69816

Gnomad4 AFR AF: 0.000400

Gnomad4 AMR AF: 0.000686

Gnomad4 ASJ AF: 0.000297

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000655

Gnomad4 FIN AF: 0.0128

Gnomad4 NFE AF: 0.00128

Gnomad4 OTH AF: 0.000500

ClinVar

Not reported in ClinVar

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;