chr10-61964631-A-G

Variant names:

• chr10-61964631-A-G
• rs7896246
• NM_032199.3:c.502+24223A>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.502+24223A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,130 control chromosomes in the GnomAD database, including 41,848 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 0.73 (41848 hom., cov: 32)
• Consequence: ARID5B NM_032199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• Publications: 12 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 (AFR) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032199.3. 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
	ARID5B	NM_032199.3	MANE Select	c.502+24223A>G		intron	N/A	NP_115575.1	Q14865-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID5B	ENST00000279873.12	TSL:1 MANE Select	c.502+24223A>G		intron	N/A	ENSP00000279873.7	Q14865-1
	ARID5B	ENST00000644638.1		c.502+24223A>G		intron	N/A	ENSP00000494412.1	A0A2R8Y5F2
	ARID5B	ENST00000681100.1		c.502+24223A>G		intron	N/A	ENSP00000506119.1	A0A7P0TAD2

Frequencies

GnomAD3 genomes AF: 0.730 AC: 111033 AN: 152012 Hom.: 41794 Cov.: 32

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.731 AC: 111141 AN: 152130 Hom.: 41848 Cov.: 32 AF XY: 0.726 AC XY: 53954 AN XY: 74354

African (AFR) AF: 0.920 AC: 38214 AN: 41544

American (AMR) AF: 0.574 AC: 8776 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2368 AN: 3468

East Asian (EAS) AF: 0.641 AC: 3311 AN: 5166

South Asian (SAS) AF: 0.508 AC: 2451 AN: 4822

European-Finnish (FIN) AF: 0.739 AC: 7807 AN: 10566

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45908 AN: 67966

Other (OTH) AF: 0.700 AC: 1475 AN: 2106

Alfa AF: 0.722 Hom.: 7471

Bravo AF: 0.727

Asia WGS AF: 0.652 AC: 2268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.87
PhyloP100		2.2
Mutation Taster		=100/0	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: rs7896246; hg19: chr10-63724390;