10-61993723-A-G

Variant names:

• chr10-61993723-A-G
• rs9415635
• NM_032199.3:c.503-6368A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032199.3(ARID5B):​c.503-6368A>G variant causes a intron change. The variant allele was found at a frequency of 0.317 in 152,078 control chromosomes in the GnomAD database, including 7,981 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (7981 hom., cov: 32)
• Consequence: ARID5B NM_032199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.03
• Publications: 6 publications found

Genes affected

ARID5B (HGNC:17362): (AT-rich interaction domain 5B) This gene encodes a member of the AT-rich interaction domain (ARID) family of DNA binding proteins. The encoded protein forms a histone H3K9Me2 demethylase complex with PHD finger protein 2 and regulates the transcription of target genes involved in adipogenesis and liver development. This gene also plays a role in cell growth and differentiation of B-lymphocyte progenitors, and single nucleotide polymorphisms in this gene are associated with acute lymphoblastic leukemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

ARID5B Gene-Disease associations (from GenCC):

• isolated cleft palate

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID5B	NM_032199.3	c.503-6368A>G		intron_variant	Intron 3 of 9	ENST00000279873.12	NP_115575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID5B	ENST00000279873.12	c.503-6368A>G		intron_variant	Intron 3 of 9	1	NM_032199.3	ENSP00000279873.7
ARID5B	ENST00000644638.1	c.503-6368A>G		intron_variant	Intron 3 of 4			ENSP00000494412.1
ARID5B	ENST00000681100.1	c.503-6368A>G		intron_variant	Intron 3 of 9			ENSP00000506119.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48185 AN: 151960 Hom.: 7974 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.334

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.317 AC: 48226 AN: 152078 Hom.: 7981 Cov.: 32 AF XY: 0.321 AC XY: 23895 AN XY: 74328

African (AFR) AF: 0.234 AC: 9730 AN: 41494

American (AMR) AF: 0.441 AC: 6735 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1084 AN: 3466

East Asian (EAS) AF: 0.365 AC: 1890 AN: 5174

South Asian (SAS) AF: 0.492 AC: 2367 AN: 4810

European-Finnish (FIN) AF: 0.288 AC: 3044 AN: 10572

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22300 AN: 67982

Other (OTH) AF: 0.333 AC: 700 AN: 2104

Alfa AF: 0.303 Hom.: 1175

Bravo AF: 0.326

Asia WGS AF: 0.358 AC: 1243 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Benign	0.90
PhyloP100		6.0
Mutation Taster		=99/1	polymorphism (auto)

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: rs9415635; hg19: chr10-63753482;