rs199948752

Variant names:

• chr6-156779214-A-G
• rs199948752
• NM_001374828.1:c.1534A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-156779214-A-G
• chr6-156779214-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001374828.1(ARID1B):​c.1534A>G​(p.Met512Val) variant causes a missense change. The variant allele was found at a frequency of 0.000707 in 1,276,488 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M512I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00058 (1 hom., cov: 30)
  • Exomes 𝑓: 0.00072 (0 hom.)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 4.10
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030590057).
• BP6: Variant 6-156779214-A-G is Benign according to our data. Variant chr6-156779214-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 126312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000576 (82/142412) while in subpopulation AMR AF = 0.0013 (19/14588). AF 95% confidence interval is 0.000852. There are 1 homozygotes in GnomAd4. There are 48 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 82 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.1534A>G	p.Met512Val	missense	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.1534A>G	p.Met512Val	missense	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.1534A>G	p.Met512Val	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.1534A>G	p.Met512Val	missense	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.1534A>G	p.Met512Val	missense	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.1534A>G	p.Met512Val	missense	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.000576 AC: 82 AN: 142296 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00130

Gnomad ASJ AF: 0.00177

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000809

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000772

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000664 AC: 83 AN: 124960 AF XY: 0.000746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000139

Gnomad ASJ exome AF: 0.00116

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000596

Gnomad NFE exome AF: 0.00110

Gnomad OTH exome AF: 0.000392

GnomAD4 exome AF: 0.000723 AC: 820 AN: 1134076 Hom.: 0 Cov.: 34 AF XY: 0.000708 AC XY: 393 AN XY: 555462

African (AFR) AF: 0.0000434 AC: 1 AN: 23020

American (AMR) AF: 0.000236 AC: 5 AN: 21144

Ashkenazi Jewish (ASJ) AF: 0.00141 AC: 22 AN: 15558

East Asian (EAS) AF: 0.00 AC: 0 AN: 24878

South Asian (SAS) AF: 0.00 AC: 0 AN: 41306

European-Finnish (FIN) AF: 0.000697 AC: 17 AN: 24394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4322

European-Non Finnish (NFE) AF: 0.000796 AC: 746 AN: 936816

Other (OTH) AF: 0.000680 AC: 29 AN: 42638

GnomAD4 genome AF: 0.000576 AC: 82 AN: 142412 Hom.: 1 Cov.: 30 AF XY: 0.000692 AC XY: 48 AN XY: 69362

African (AFR) AF: 0.00 AC: 0 AN: 39082

American (AMR) AF: 0.00130 AC: 19 AN: 14588

Ashkenazi Jewish (ASJ) AF: 0.00177 AC: 6 AN: 3382

East Asian (EAS) AF: 0.00 AC: 0 AN: 4450

South Asian (SAS) AF: 0.00 AC: 0 AN: 4424

European-Finnish (FIN) AF: 0.000809 AC: 7 AN: 8658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.000773 AC: 50 AN: 64722

Other (OTH) AF: 0.00 AC: 0 AN: 1986

Alfa AF: 0.000695 Hom.: 1

Bravo AF: 0.000465

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000422 AC: 3

ExAC AF: 0.000626 AC: 71

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	1	ARID1B-related disorder (1)
-	-	1	Coffin-Siris syndrome 1 (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	23
DANN	Benign	0.54
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.1
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.11
Sift	Benign	0.054	T
Sift4G	Benign	0.11	T
Polyphen		0.78	P
Vest4		0.30
MVP		0.19
MPC		0.32
ClinPred		0.049	T
GERP RS		2.2
PromoterAI		-0.012	Neutral
Varity_R		0.25
gMVP		0.60
Mutation Taster		=90/10	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: rs199948752; hg19: chr6-157100348;