rs10994983

Variant names:

• chr10-61953068-G-C
• rs10994983
• NM_032199.3:c.502+12660G>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.502+12660G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 151,780 control chromosomes in the GnomAD database, including 406 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 0.064 (406 hom., cov: 32)
• Consequence: ARID5B NM_032199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• 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=-0.54).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID5B	NM_032199.3	c.502+12660G>C		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.502+12660G>C		intron_variant	Intron 3 of 9	1	NM_032199.3	ENSP00000279873.7
ARID5B	ENST00000644638.1	c.502+12660G>C		intron_variant	Intron 3 of 4			ENSP00000494412.1
ARID5B	ENST00000681100.1	c.502+12660G>C		intron_variant	Intron 3 of 9			ENSP00000506119.1

Frequencies

GnomAD3 genomes AF: 0.0645 AC: 9778 AN: 151664 Hom.: 406 Cov.: 32

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0441

Gnomad ASJ AF: 0.0969

Gnomad EAS AF: 0.0322

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0870

Gnomad OTH AF: 0.0674

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

GnomAD4 genome AF: 0.0644 AC: 9777 AN: 151780 Hom.: 406 Cov.: 32 AF XY: 0.0633 AC XY: 4694 AN XY: 74142

African (AFR) AF: 0.0284 AC: 1175 AN: 41340

American (AMR) AF: 0.0441 AC: 672 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0969 AC: 336 AN: 3466

East Asian (EAS) AF: 0.0321 AC: 166 AN: 5176

South Asian (SAS) AF: 0.122 AC: 584 AN: 4788

European-Finnish (FIN) AF: 0.0670 AC: 704 AN: 10500

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0870 AC: 5909 AN: 67950

Other (OTH) AF: 0.0672 AC: 142 AN: 2112

Alfa AF: 0.0789 Hom.: 71

Bravo AF: 0.0600

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.46
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10994983; hg19: chr10-63712827;