NM_001374828.1:c.1624G>C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001374828.1(ARID1B):c.1624G>C(p.Ala542Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000687 in 145,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A542T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 30)

Consequence

ARID1B
NM_001374828.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.796

Publications

0 publications found

Variant links:

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

ARID1B links:

ENSG00000296922 (HGNC:):

ENSG00000296922 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16988835).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARID1B	NM_001374828.1	MANE Select	c.1624G>C	p.Ala542Pro	missense	Exon 1 of 20	NP_001361757.1
ARID1B	NM_001438482.1		c.1624G>C	p.Ala542Pro	missense	Exon 1 of 21	NP_001425411.1
ARID1B	NM_001438483.1		c.1624G>C	p.Ala542Pro	missense	Exon 1 of 21	NP_001425412.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.1624G>C	p.Ala542Pro	missense	Exon 1 of 20	ENSP00000490491.2
ARID1B	ENST00000346085.10	TSL:1	c.1624G>C	p.Ala542Pro	missense	Exon 2 of 21	ENSP00000344546.5
ARID1B	ENST00000350026.11	TSL:1	c.1624G>C	p.Ala542Pro	missense	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes

AF:

0.00000687

AC:

AN:

145632

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000687

AC:

AN:

145632

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70964

show subpopulations

African (AFR)

AF:

0.0000248

AC:

AN:

40368

American (AMR)

AF:

0.00

AC:

AN:

14750

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3400

East Asian (EAS)

AF:

0.00

AC:

AN:

4890

South Asian (SAS)

AF:

0.00

AC:

AN:

4760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8650

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65608

Other (OTH)

AF:

0.00

AC:

AN:

2028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.014

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.81

MutationAssessor

Benign

-0.34

PhyloP100

0.80

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.46

REVEL

Benign

0.085

Sift

Benign

0.42

Sift4G

Benign

0.26

Polyphen

0.92

Vest4

0.17

MutPred

0.29

Gain of loop (P = 0.0051)

MVP

0.33

MPC

0.38

ClinPred

0.49

GERP RS

1.5

PromoterAI

0.030

Neutral

(source)

Varity_R

0.15

gMVP

0.30

Mutation Taster

=83/17

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over