10-62070527-T-C

Variant names:

• chr10-62070527-T-C
• rs7090871
• NM_032199.3:c.1199+730T>C

Variant summary

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

The NM_032199.3(ARID5B):​c.1199+730T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,124 control chromosomes in the GnomAD database, including 9,005 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 0.33 (9005 hom., cov: 32)
• Consequence: ARID5B NM_032199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID5B	NM_032199.3	c.1199+730T>C		intron_variant	Intron 8 of 9	ENST00000279873.12	NP_115575.1
ARID5B	NM_001244638.2	c.470+730T>C		intron_variant	Intron 5 of 6		NP_001231567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID5B	ENST00000279873.12	c.1199+730T>C		intron_variant	Intron 8 of 9	1	NM_032199.3	ENSP00000279873.7
ARID5B	ENST00000681100.1	c.1175+730T>C		intron_variant	Intron 8 of 9			ENSP00000506119.1
ARID5B	ENST00000309334.5	c.470+730T>C		intron_variant	Intron 5 of 6	5		ENSP00000308862.5

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50172 AN: 152006 Hom.: 9011 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.330 AC: 50158 AN: 152124 Hom.: 9005 Cov.: 32 AF XY: 0.328 AC XY: 24370 AN XY: 74352

African (AFR) AF: 0.187 AC: 7753 AN: 41526

American (AMR) AF: 0.316 AC: 4832 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3470

East Asian (EAS) AF: 0.349 AC: 1805 AN: 5172

South Asian (SAS) AF: 0.362 AC: 1746 AN: 4824

European-Finnish (FIN) AF: 0.392 AC: 4142 AN: 10566

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27595 AN: 67974

Other (OTH) AF: 0.309 AC: 653 AN: 2114

Alfa AF: 0.371 Hom.: 21882

Bravo AF: 0.315

Asia WGS AF: 0.335 AC: 1164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		0.68
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: rs7090871; hg19: chr10-63830286;