rs797045270

Positions:

• chr6-156779308-C-G
• chr6-156779308-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001374828.1(ARID1B):​c.1628C>G​(p.Ala543Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000494 in 972,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. A543V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000049 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.811

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.098498076).
• BS2: High AC in GnomAdExome4 at 48 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.1628C>G	p.Ala543Gly	missense_variant	1/20	ENST00000636930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.1628C>G	p.Ala543Gly	missense_variant	1/20	2	NM_001374828.1	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 144550 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.00

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 AF: 0.0000494 AC: 48 AN: 972348 Hom.: 0 Cov.: 33 AF XY: 0.0000610 AC XY: 28 AN XY: 458658

Gnomad4 AFR exome AF: 0.000105

Gnomad4 AMR exome AF: 0.000203

Gnomad4 ASJ exome AF: 0.000314

Gnomad4 EAS exome AF: 0.000175

Gnomad4 SAS exome AF: 0.000108

Gnomad4 FIN exome AF: 0.000273

Gnomad4 NFE exome AF: 0.0000388

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 144550 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 70408

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Benign	0.82
DEOGEN2	Benign	0.014	.;T;.;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.46	T;T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.098	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.0	.;N;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.38	.;N;.;.
REVEL	Benign	0.070
Sift	Benign	0.093	.;T;.;.
Sift4G	Benign	0.061	.;T;.;.
Polyphen		0.0	.;B;.;B
Vest4		0.15
MutPred		0.26		.;Loss of helix (P = 0.0304);Loss of helix (P = 0.0304);Loss of helix (P = 0.0304);
MVP		0.11
MPC		0.40
ClinPred		0.13	T
GERP RS		-0.66
Varity_R		0.11
gMVP		0.13

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

LitVar

Other links and lift over

dbSNP: rs797045270; hg19: chr6-157100442; COSMIC: COSV51667793; COSMIC: COSV51667793;