10-62054311-A-T

Variant names:

• chr10-62054311-A-T
• rs725529
• NM_032199.3:c.847-2806A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032199.3(ARID5B):​c.847-2806A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,000 control chromosomes in the GnomAD database, including 11,404 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 0.38 (11404 hom., cov: 31)
• Consequence: ARID5B NM_032199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 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.847-2806A>T		intron	N/A	NP_115575.1	Q14865-1
	ARID5B	NM_001244638.2		c.118-2806A>T		intron	N/A	NP_001231567.1	Q14865-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID5B	ENST00000279873.12	TSL:1 MANE Select	c.847-2806A>T		intron	N/A	ENSP00000279873.7	Q14865-1
	ARID5B	ENST00000681100.1		c.847-2806A>T		intron	N/A	ENSP00000506119.1	A0A7P0TAD2
	ARID5B	ENST00000309334.5	TSL:5	c.118-2806A>T		intron	N/A	ENSP00000308862.5	Q14865-2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57724 AN: 151880 Hom.: 11391 Cov.: 31

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.380 AC: 57770 AN: 152000 Hom.: 11404 Cov.: 31 AF XY: 0.390 AC XY: 28945 AN XY: 74292

African (AFR) AF: 0.312 AC: 12951 AN: 41446

American (AMR) AF: 0.373 AC: 5693 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3468

East Asian (EAS) AF: 0.504 AC: 2599 AN: 5156

South Asian (SAS) AF: 0.465 AC: 2239 AN: 4818

European-Finnish (FIN) AF: 0.511 AC: 5397 AN: 10562

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25924 AN: 67956

Other (OTH) AF: 0.414 AC: 876 AN: 2114

Alfa AF: 0.241 Hom.: 570

Bravo AF: 0.368

Asia WGS AF: 0.507 AC: 1763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		2.0
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: rs725529; hg19: chr10-63814070;