rs10821944

Variant names:

• chr10-62025330-G-T
• rs10821944
• ENST00000644638.1:c.*626G>T

Variant summary

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

The ENST00000644638.1(ARID5B):​c.*626G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,026 control chromosomes in the GnomAD database, including 33,858 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 0.66 (33858 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: ARID5B ENST00000644638.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 38 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID5B	NM_032199.3	c.733+25009G>T		intron_variant	Intron 4 of 9	ENST00000279873.12	NP_115575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID5B	ENST00000644638.1	c.*626G>T		3_prime_UTR_variant	Exon 5 of 5			ENSP00000494412.1
ARID5B	ENST00000279873.12	c.733+25009G>T		intron_variant	Intron 4 of 9	1	NM_032199.3	ENSP00000279873.7
ARID5B	ENST00000681100.1	c.733+25009G>T		intron_variant	Intron 4 of 9			ENSP00000506119.1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100682 AN: 151908 Hom.: 33871 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.645

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.662 AC: 100694 AN: 152026 Hom.: 33858 Cov.: 31 AF XY: 0.662 AC XY: 49196 AN XY: 74300

African (AFR) AF: 0.559 AC: 23183 AN: 41452

American (AMR) AF: 0.582 AC: 8885 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2288 AN: 3472

East Asian (EAS) AF: 0.698 AC: 3609 AN: 5168

South Asian (SAS) AF: 0.672 AC: 3236 AN: 4818

European-Finnish (FIN) AF: 0.736 AC: 7772 AN: 10562

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.727 AC: 49405 AN: 67966

Other (OTH) AF: 0.642 AC: 1355 AN: 2112

Alfa AF: 0.698 Hom.: 125845

Bravo AF: 0.645

Asia WGS AF: 0.612 AC: 2129 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	15
DANN	Benign	0.62
PhyloP100		1.3
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: rs10821944; hg19: chr10-63785089;