NM_001374828.1:c.367_372dupTCCTCC

Variant names:

• chr6-156778031-G-GTCCTCC
• rs770512547
• NM_001374828.1:c.367_372dupTCCTCC

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BS1 BS2

The NM_001374828.1(ARID1B):​c.367_372dupTCCTCC​(p.Ser123_Ser124dup) variant causes a conservative 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 conservative_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.109
• 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: Benign. The variant received -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. GnomAdExome4 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 GnomAdExome4. There are 99 alleles in the male GnomAdExome4 subpopulation. Median coverage is 35. This position passed quality control check.
• BS2: High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID1B	NM_001374828.1	c.367_372dupTCCTCC	p.Ser123_Ser124dup	conservative_inframe_insertion	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.367_372dupTCCTCC	p.Ser123_Ser124dup	conservative_inframe_insertion	Exon 1 of 20	2	NM_001374828.1	ENSP00000490491.2

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

GnomAD2 exomes AF: 0.000179 AC: 19 AN: 106066 AF XY: 0.000208

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 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

African (AFR) AF: 0.0000319 AC: 1 AN: 31384

American (AMR) AF: 0.0000281 AC: 1 AN: 35524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25098

East Asian (EAS) AF: 0.0000561 AC: 2 AN: 35654

South Asian (SAS) AF: 0.000772 AC: 61 AN: 78994

European-Finnish (FIN) AF: 0.0000280 AC: 1 AN: 35748

Middle Eastern (MID) AF: 0.000588 AC: 3 AN: 5098

European-Non Finnish (NFE) AF: 0.0000901 AC: 97 AN: 1077062

Other (OTH) AF: 0.000173 AC: 10 AN: 57736

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

African (AFR) AF: 0.00 AC: 0 AN: 41124

American (AMR) AF: 0.000264 AC: 4 AN: 15176

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4994

South Asian (SAS) AF: 0.000418 AC: 2 AN: 4782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000894 AC: 6 AN: 67118

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.0000364 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Oct 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 01, 2020

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11
Mutation Taster		=89/11	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;