6-156778031-GTCCTCCTCC-GTCCTCCTCCTCCTCC

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BS1 BS2

The NM_001374828.1(ARID1B):c.367_372dup(p.Ser123_Ser124dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,532,506 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000087 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: ARID1B NM_001374828.1 inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.109

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 -14 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001374828.1.
• BP6: Variant 6-156778031-G-GTCCTCC is Benign according to our data. Variant chr6-156778031-G-GTCCTCC is described in ClinVar as [Likely_benign]. Clinvar id is 872671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000127 (176/1382298) while in subpopulation SAS AF= 0.000772 (61/78994). AF 95% confidence interval is 0.000617. There are 1 homozygotes in gnomad4_exome. There are 99 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck.
• BS2: High AC in GnomAd at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.367_372dup	p.Ser123_Ser124dup	inframe_insertion	1/20	ENST00000636930.2
LOC115308161	NR_163974.1	n.273+214_273+215insGGAGGA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.367_372dup	p.Ser123_Ser124dup	inframe_insertion	1/20	2	NM_001374828.1	A2
	ENST00000603191.2	n.177+214_177+215insGGAGGA		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0000866 AC: 13 AN: 150102 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000264

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000418

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000894

Gnomad OTH AF: 0.000484

GnomAD3 exomes AF: 0.000179 AC: 19 AN: 106066 Hom.: 0 AF XY: 0.000208 AC XY: 12 AN XY: 57628

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000493

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000237

Gnomad SAS exome AF: 0.000672

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000761

Gnomad OTH exome AF: 0.000303

GnomAD4 exome AF: 0.000127 AC: 176 AN: 1382298 Hom.: 1 Cov.: 35 AF XY: 0.000145 AC XY: 99 AN XY: 681924

Gnomad4 AFR exome AF: 0.0000319

Gnomad4 AMR exome AF: 0.0000281

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000561

Gnomad4 SAS exome AF: 0.000772

Gnomad4 FIN exome AF: 0.0000280

Gnomad4 NFE exome AF: 0.0000901

Gnomad4 OTH exome AF: 0.000173

GnomAD4 genome AF: 0.0000865 AC: 13 AN: 150208 Hom.: 0 Cov.: 31 AF XY: 0.000109 AC XY: 8 AN XY: 73360

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000264

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000418

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000894

Gnomad4 OTH AF: 0.000479

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 12, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2020	- -

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: rs770512547; hg19: chr6-157099165;