6-156778031-GTCCTCCTCC-GTCC

Variant names:

• chr6-156778031-GTCCTCC-G
• rs770512547
• NM_001374828.1:c.367_372delTCCTCC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM4 BS2_Supporting

The NM_001374828.1(ARID1B):​c.367_372delTCCTCC​(p.Ser123_Ser124del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000163 in 1,532,364 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. S123S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: ARID1B NM_001374828.1 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.00
• Publications: 0 publications found

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]

ARID1B Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina, ClinGen
• Coffin-Siris syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000271551 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001374828.1.
• BS2: High AC in GnomAd4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374828.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	NM_001374828.1	MANE Select	c.367_372delTCCTCC	p.Ser123_Ser124del	conservative_inframe_deletion	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.367_372delTCCTCC	p.Ser123_Ser124del	conservative_inframe_deletion	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.367_372delTCCTCC	p.Ser123_Ser124del	conservative_inframe_deletion	Exon 1 of 21	NP_001425412.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.367_372delTCCTCC	p.Ser123_Ser124del	conservative_inframe_deletion	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.367_372delTCCTCC	p.Ser123_Ser124del	conservative_inframe_deletion	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.367_372delTCCTCC	p.Ser123_Ser124del	conservative_inframe_deletion	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.0000400 AC: 6 AN: 150100 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000200

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000943 AC: 1 AN: 106066 AF XY: 0.0000174

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000195

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 19 AN: 1382264 Hom.: 0 AF XY: 0.0000117 AC XY: 8 AN XY: 681904

African (AFR) AF: 0.0000956 AC: 3 AN: 31382

American (AMR) AF: 0.00 AC: 0 AN: 35524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25096

East Asian (EAS) AF: 0.00 AC: 0 AN: 35654

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 78992

European-Finnish (FIN) AF: 0.0000280 AC: 1 AN: 35746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5096

European-Non Finnish (NFE) AF: 0.00000836 AC: 9 AN: 1077038

Other (OTH) AF: 0.0000693 AC: 4 AN: 57736

GnomAD4 genome AF: 0.0000400 AC: 6 AN: 150100 Hom.: 0 Cov.: 30 AF XY: 0.0000273 AC XY: 2 AN XY: 73242

African (AFR) AF: 0.000122 AC: 5 AN: 41008

American (AMR) AF: 0.00 AC: 0 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.000200 AC: 1 AN: 5010

South Asian (SAS) AF: 0.00 AC: 0 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67130

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=167/33	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs770512547; hg19: chr6-157099165; COSMIC: COSV107293338; COSMIC: COSV107293338;