rs114201726

Variant names:

• chr6-157133075-C-T
• rs114201726
• NM_001374828.1:c.2629C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001374828.1(ARID1B):​c.2629C>T​(p.Pro877Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,613,860 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00097 (14 hom.)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.45
• Publications: 4 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: Illumina, ClinGen, Orphanet
• Coffin-Siris syndrome 1

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004647851).
• BP6: Variant 6-157133075-C-T is Benign according to our data. Variant chr6-157133075-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00671 (1022/152244) while in subpopulation AFR AF = 0.0225 (933/41532). AF 95% confidence interval is 0.0213. There are 14 homozygotes in GnomAd4. There are 461 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1022 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	NM_001374828.1	MANE Select	c.2629C>T	p.Pro877Ser	missense	Exon 7 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.2629C>T	p.Pro877Ser	missense	Exon 7 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.2671C>T	p.Pro891Ser	missense	Exon 8 of 21	NP_001425412.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.2629C>T	p.Pro877Ser	missense	Exon 7 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.2668C>T	p.Pro890Ser	missense	Exon 9 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.2629C>T	p.Pro877Ser	missense	Exon 7 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.00669 AC: 1018 AN: 152126 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00221 AC: 554 AN: 251094 AF XY: 0.00187

Gnomad AFR exome AF: 0.0209

Gnomad AMR exome AF: 0.00128

Gnomad ASJ exome AF: 0.0135

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.000966 AC: 1412 AN: 1461616 Hom.: 14 Cov.: 30 AF XY: 0.000908 AC XY: 660 AN XY: 727110

African (AFR) AF: 0.0218 AC: 728 AN: 33454

American (AMR) AF: 0.00112 AC: 50 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.0140 AC: 366 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5764

European-Non Finnish (NFE) AF: 0.0000773 AC: 86 AN: 1111932

Other (OTH) AF: 0.00278 AC: 168 AN: 60386

GnomAD4 genome AF: 0.00671 AC: 1022 AN: 152244 Hom.: 14 Cov.: 32 AF XY: 0.00619 AC XY: 461 AN XY: 74458

African (AFR) AF: 0.0225 AC: 933 AN: 41532

American (AMR) AF: 0.00111 AC: 17 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68012

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.00318 Hom.: 7

Bravo AF: 0.00744

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0222 AC: 98

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00236 AC: 287

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000534

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Coffin-Siris syndrome 1 (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Benign	0.77
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.012
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.63	N
PhyloP100		2.5
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.088
Sift	Uncertain	0.0020	D
Sift4G	Benign	1.0	T
Polyphen		0.022	B
Vest4		0.29
MVP		0.33
MPC		0.35
ClinPred		0.013	T
GERP RS		6.0
Varity_R		0.043
gMVP		0.21
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs114201726; hg19: chr6-157454209; COSMIC: COSV99034324;