rs797045266

Variant names:

• chr6-156777927-A-C
• rs797045266
• NM_001374828.1:c.247A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-156777927-A-C
• chr6-156777927-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001374828.1(ARID1B):​c.247A>C​(p.Asn83His) variant causes a missense change. The variant allele was found at a frequency of 0.00000671 in 148,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/7 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. N83D) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000067 (0 hom., cov: 31)
• Consequence: ARID1B NM_001374828.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.79
• 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: 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35129678).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	NM_001374828.1	MANE Select	c.247A>C	p.Asn83His	missense	Exon 1 of 20	NP_001361757.1
	ARID1B	NM_001438482.1		c.247A>C	p.Asn83His	missense	Exon 1 of 21	NP_001425411.1
	ARID1B	NM_001438483.1		c.247A>C	p.Asn83His	missense	Exon 1 of 21	NP_001425412.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.247A>C	p.Asn83His	missense	Exon 1 of 20	ENSP00000490491.2
	ARID1B	ENST00000346085.10	TSL:1	c.247A>C	p.Asn83His	missense	Exon 2 of 21	ENSP00000344546.5
	ARID1B	ENST00000350026.11	TSL:1	c.247A>C	p.Asn83His	missense	Exon 1 of 19	ENSP00000055163.8

Frequencies

GnomAD3 genomes AF: 0.00000672 AC: 1 AN: 148844 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.00000671 AC: 1 AN: 148946 Hom.: 0 Cov.: 31 AF XY: 0.0000137 AC XY: 1 AN XY: 72768

African (AFR) AF: 0.00 AC: 0 AN: 40508

American (AMR) AF: 0.00 AC: 0 AN: 15074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 4934

South Asian (SAS) AF: 0.00 AC: 0 AN: 4718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66814

Other (OTH) AF: 0.00 AC: 0 AN: 2076

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_noAF	Benign	-0.66
CADD	Benign	21
DANN	Benign	0.36
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.35	T
PhyloP100		3.8
GERP RS		2.5
PromoterAI		-0.50	Neutral

Splicing

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

Other links and lift over

dbSNP: rs797045266; hg19: chr6-157099061;