rs878853084

Variant names:

• chr6-156778948-C-T
• rs878853084
• NM_001374828.1:c.1268C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-156778948-C-T
• chr6-156778948-C-A
• chr6-156778948-C-G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001374828.1(ARID1B):​c.1268C>T​(p.Ala423Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,282,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 2.14
• 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)

ENSG00000296922 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02032873).
• BP6: Variant 6-156778948-C-T is Benign according to our data. Variant chr6-156778948-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 235645.
• BS2: High AC in GnomAd4 at 15 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.1268C>T	p.Ala423Val	missense	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.1268C>T	p.Ala423Val	missense	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.1268C>T	p.Ala423Val	missense	Exon 1 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.1268C>T	p.Ala423Val	missense	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.1268C>T	p.Ala423Val	missense	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.1268C>T	p.Ala423Val	missense	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.000103 AC: 15 AN: 145190 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.0106

Gnomad AMR AF: 0.0000674

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000761

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000114 AC: 13 AN: 1137652 Hom.: 0 Cov.: 35 AF XY: 0.0000128 AC XY: 7 AN XY: 548416

African (AFR) AF: 0.00 AC: 0 AN: 23152

American (AMR) AF: 0.00 AC: 0 AN: 8820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14936

East Asian (EAS) AF: 0.00 AC: 0 AN: 26948

South Asian (SAS) AF: 0.00 AC: 0 AN: 28190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3260

European-Non Finnish (NFE) AF: 0.0000136 AC: 13 AN: 957896

Other (OTH) AF: 0.00 AC: 0 AN: 45958

GnomAD4 genome AF: 0.000103 AC: 15 AN: 145190 Hom.: 0 Cov.: 29 AF XY: 0.0000845 AC XY: 6 AN XY: 70974

African (AFR) AF: 0.00 AC: 0 AN: 39316

American (AMR) AF: 0.0000674 AC: 1 AN: 14828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 4720

South Asian (SAS) AF: 0.00 AC: 0 AN: 4552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.0000761 AC: 5 AN: 65670

Other (OTH) AF: 0.00 AC: 0 AN: 1966

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.1
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.041
Sift	Benign	0.091	T
Sift4G	Benign	0.099	T
Polyphen		0.24	B
Vest4		0.25
MutPred		0.37		Gain of catalytic residue at A340 (P = 0.0087)
MVP		0.12
MPC		0.29
ClinPred		0.14	T
GERP RS		1.4
PromoterAI		0.029	Neutral
Varity_R		0.074
gMVP		0.17
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs878853084; hg19: chr6-157100082; COSMIC: COSV99034260;