rs776745618

Variant names:

• chr6-156778126-A-G
• rs776745618
• NM_001374828.1:c.446A>G
• ARID1B p.Asn149Ser

Your query was ambiguous. Multiple possible variants found:

• chr6-156778126-A-G
• chr6-156778126-A-C
• chr6-156778126-A-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BS1 BS2

The NM_001374828.1(ARID1B):​c.446A>G​(p.Asn149Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,538,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:5
• Conservation: PhyloP100: 1.24
• Publications: 9 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: Orphanet, Illumina, ClinGen
• Coffin-Siris syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000271551 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15886977).
• BP6: Variant 6-156778126-A-G is Benign according to our data. Variant chr6-156778126-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 210272.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000235 (327/1389998) while in subpopulation EAS AF = 0.00042 (15/35720). AF 95% confidence interval is 0.000258. There are 0 homozygotes in GnomAdExome4. There are 160 alleles in the male GnomAdExome4 subpopulation. Median coverage is 36. This position passed quality control check.
• BS2: High AC in GnomAd4 at 28 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.446A>G	p.Asn149Ser	missense	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.446A>G	p.Asn149Ser	missense	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.446A>G	p.Asn149Ser	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.446A>G	p.Asn149Ser	missense	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.446A>G	p.Asn149Ser	missense	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.446A>G	p.Asn149Ser	missense	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.000188 AC: 28 AN: 148876 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000993

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000411

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000284

Gnomad OTH AF: 0.000484

GnomAD2 exomes AF: 0.000137 AC: 19 AN: 138974 AF XY: 0.000107

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.0000407

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000553

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000235 AC: 327 AN: 1389998 Hom.: 0 Cov.: 36 AF XY: 0.000233 AC XY: 160 AN XY: 685882

African (AFR) AF: 0.0000317 AC: 1 AN: 31568

American (AMR) AF: 0.0000560 AC: 2 AN: 35692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.000420 AC: 15 AN: 35720

South Asian (SAS) AF: 0.00 AC: 0 AN: 79176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5164

European-Non Finnish (NFE) AF: 0.000279 AC: 301 AN: 1078814

Other (OTH) AF: 0.000138 AC: 8 AN: 57878

GnomAD4 genome AF: 0.000188 AC: 28 AN: 148876 Hom.: 0 Cov.: 31 AF XY: 0.000179 AC XY: 13 AN XY: 72634

African (AFR) AF: 0.0000993 AC: 4 AN: 40274

American (AMR) AF: 0.000132 AC: 2 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3426

East Asian (EAS) AF: 0.000411 AC: 2 AN: 4870

South Asian (SAS) AF: 0.00 AC: 0 AN: 4688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.000284 AC: 19 AN: 66920

Other (OTH) AF: 0.000484 AC: 1 AN: 2064

Alfa AF: 0.000238 Hom.: 0

Bravo AF: 0.000234

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	3	not provided (4)
-	-	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	0.12
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Benign	0.88
DEOGEN2	Benign	0.019	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.69	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.2
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Benign	1.0	T
PromoterAI		-0.0042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.28
gMVP		0.31
Mutation Taster		=77/23	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs776745618;

hg19: chr6-157099260;

COSMIC: COSV99034296;