rs1270815175

Variant names:

• chr6-156777723-C-G
• rs1270815175
• NM_001374828.1:c.43C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-156777723-C-G
• chr6-156777723-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001374828.1(ARID1B):​c.43C>G​(p.Arg15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000868 in 138,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/6 in silico tools predict 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. R15P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000087 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.780
• Publications: 0 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042066127).
• BP6: Variant 6-156777723-C-G is Benign according to our data. Variant chr6-156777723-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3341877.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 12 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.43C>G	p.Arg15Gly	missense	Exon 1 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.43C>G	p.Arg15Gly	missense	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.43C>G	p.Arg15Gly	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.43C>G	p.Arg15Gly	missense	Exon 1 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.43C>G	p.Arg15Gly	missense	Exon 2 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.43C>G	p.Arg15Gly	missense	Exon 1 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.0000868 AC: 12 AN: 138318 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00336

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000160

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 24924 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 11906

African (AFR) AF: 0.00 AC: 0 AN: 460

American (AMR) AF: 0.00 AC: 0 AN: 30

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 142

East Asian (EAS) AF: 0.00 AC: 0 AN: 74

South Asian (SAS) AF: 0.00 AC: 0 AN: 538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 46

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 22840

Other (OTH) AF: 0.00 AC: 0 AN: 790

GnomAD4 genome AF: 0.0000868 AC: 12 AN: 138318 Hom.: 0 Cov.: 31 AF XY: 0.000104 AC XY: 7 AN XY: 67150

African (AFR) AF: 0.00 AC: 0 AN: 38634

American (AMR) AF: 0.00 AC: 0 AN: 14134

Ashkenazi Jewish (ASJ) AF: 0.00336 AC: 11 AN: 3278

East Asian (EAS) AF: 0.00 AC: 0 AN: 4614

South Asian (SAS) AF: 0.00 AC: 0 AN: 4500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 244

European-Non Finnish (NFE) AF: 0.0000160 AC: 1 AN: 62520

Other (OTH) AF: 0.00 AC: 0 AN: 1868

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_noAF	Benign	-0.73
CADD	Benign	18
DANN	Benign	0.33
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.042	T
PhyloP100		-0.78
PromoterAI		-0.055	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1270815175; hg19: chr6-157098857;