rs112703040

Variant names:

• chr6-157207063-C-T
• rs112703040
• NM_001374828.1:c.6291C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-157207063-C-T
• chr6-157207063-C-A
• chr6-157207063-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001374828.1(ARID1B):​c.6291C>T​(p.Ile2097Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00937 in 1,614,160 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0081 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0095 (99 hom.)
• Consequence: ARID1B NM_001374828.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.33
• Publications: 5 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)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 6-157207063-C-T is Benign according to our data. Variant chr6-157207063-C-T is described in ClinVar as Benign. ClinVar VariationId is 126336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.33 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00814 (1240/152270) while in subpopulation NFE AF = 0.0117 (794/68018). AF 95% confidence interval is 0.011. There are 10 homozygotes in GnomAd4. There are 574 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1240 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.6291C>T	p.Ile2097Ile	synonymous	Exon 20 of 20	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.6420C>T	p.Ile2140Ile	synonymous	Exon 21 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.6333C>T	p.Ile2111Ile	synonymous	Exon 21 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.6291C>T	p.Ile2097Ile	synonymous	Exon 20 of 20	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.6171C>T	p.Ile2057Ile	synonymous	Exon 21 of 21	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.6132C>T	p.Ile2044Ile	synonymous	Exon 19 of 19	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.00814 AC: 1239 AN: 152152 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.00936

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00933

Gnomad FIN AF: 0.00981

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.00814

GnomAD2 exomes AF: 0.00991 AC: 2489 AN: 251250 AF XY: 0.0106

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.00682

Gnomad ASJ exome AF: 0.00586

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0122

Gnomad NFE exome AF: 0.0125

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.00950 AC: 13881 AN: 1461890 Hom.: 99 Cov.: 31 AF XY: 0.00980 AC XY: 7127 AN XY: 727246

African (AFR) AF: 0.00140 AC: 47 AN: 33480

American (AMR) AF: 0.00693 AC: 310 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00620 AC: 162 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0132 AC: 1142 AN: 86258

European-Finnish (FIN) AF: 0.0114 AC: 607 AN: 53416

Middle Eastern (MID) AF: 0.0199 AC: 115 AN: 5768

European-Non Finnish (NFE) AF: 0.00983 AC: 10934 AN: 1112012

Other (OTH) AF: 0.00932 AC: 563 AN: 60396

GnomAD4 genome AF: 0.00814 AC: 1240 AN: 152270 Hom.: 10 Cov.: 32 AF XY: 0.00771 AC XY: 574 AN XY: 74456

African (AFR) AF: 0.00202 AC: 84 AN: 41568

American (AMR) AF: 0.00934 AC: 143 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00955 AC: 46 AN: 4818

European-Finnish (FIN) AF: 0.00981 AC: 104 AN: 10600

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0117 AC: 794 AN: 68018

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.00882 Hom.: 6

Bravo AF: 0.00783

Asia WGS AF: 0.00837 AC: 29 AN: 3478

EpiCase AF: 0.0157

EpiControl AF: 0.0140

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	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
BayesDel_noAF	Benign	-0.34
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		1.3
PromoterAI		-0.0072	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	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: rs112703040; hg19: chr6-157528197; COSMIC: COSV51650817;