NM_001374828.1:c.253G>A

Variant names:

• chr6-156777933-G-A
• rs1349412123
• NM_001374828.1:c.253G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001374828.1(ARID1B):​c.253G>A​(p.Ala85Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. A85S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.36
• Publications: 2 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)

ENSG00000271551 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41447836).

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.253G>A	p.Ala85Thr	missense	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.253G>A	p.Ala85Thr	missense	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.253G>A	p.Ala85Thr	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.253G>A	p.Ala85Thr	missense	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.253G>A	p.Ala85Thr	missense	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.253G>A	p.Ala85Thr	missense	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1376900 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 679232

African (AFR) AF: 0.00 AC: 0 AN: 31240

American (AMR) AF: 0.00 AC: 0 AN: 34876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24880

East Asian (EAS) AF: 0.00 AC: 0 AN: 35568

South Asian (SAS) AF: 0.00 AC: 0 AN: 78594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4082

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076626

Other (OTH) AF: 0.00 AC: 0 AN: 57456

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Benign	0.90
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.084
Eigen_PC	Benign	-0.052
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.4
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.11	T
Vest4		0.20
MutPred		0.22		Gain of glycosylation at A2 (P = 0.0016)
MVP		0.22
MPC		0.28
ClinPred		0.53	D
GERP RS		2.5
PromoterAI		-0.30	Neutral
Varity_R		0.29
gMVP		0.45
Mutation Taster		=81/19	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: rs1349412123; hg19: chr6-157099067;