chr6-157206821-C-A

Position:

• chr6-157206821-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001374828.1(ARID1B):​c.6049C>A​(p.Pro2017Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. P2017S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09534371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID1B	NM_001374828.1	c.6049C>A	p.Pro2017Thr	missense_variant	20/20	ENST00000636930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID1B	ENST00000636930.2	c.6049C>A	p.Pro2017Thr	missense_variant	20/20	2	NM_001374828.1	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461778 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727190

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.029	.;T;.;.;T;.;T;.;.;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.095	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	.;M;.;.;.;.;.;.;.;.
MutationTaster	Benign	0.80	N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.20	.;N;.;.;N;.;.;.;.;.
REVEL	Benign	0.031
Sift	Benign	0.076	.;T;.;.;T;.;.;.;.;.
Sift4G	Benign	0.38	.;T;.;.;T;.;.;.;.;.
Polyphen		0.029, 0.050	.;B;.;B;.;.;.;.;.;.
Vest4		0.19
MutPred		0.12		.;Gain of phosphorylation at P1881 (P = 0.0275);.;.;.;.;.;.;.;.;
MVP		0.33
MPC		0.73
ClinPred		0.10	T
GERP RS		3.1
Varity_R		0.037
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-157527955;