10-61963818-C-T

Variant names:

• chr10-61963818-C-T
• rs10821936
• NM_032199.3:c.502+23410C>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.502+23410C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 151,362 control chromosomes in the GnomAD database, including 36,226 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 0.69 (36226 hom., cov: 28)
• Consequence: ARID5B NM_032199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840
• Publications: 97 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID5B	NM_032199.3	c.502+23410C>T		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+23410C>T		intron_variant	Intron 3 of 9	1	NM_032199.3	ENSP00000279873.7
ARID5B	ENST00000644638.1	c.502+23410C>T		intron_variant	Intron 3 of 4			ENSP00000494412.1
ARID5B	ENST00000681100.1	c.502+23410C>T		intron_variant	Intron 3 of 9			ENSP00000506119.1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104006 AN: 151240 Hom.: 36181 Cov.: 28

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.688 AC: 104108 AN: 151362 Hom.: 36226 Cov.: 28 AF XY: 0.684 AC XY: 50567 AN XY: 73898

African (AFR) AF: 0.774 AC: 31915 AN: 41242

American (AMR) AF: 0.557 AC: 8417 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2363 AN: 3464

East Asian (EAS) AF: 0.638 AC: 3282 AN: 5142

South Asian (SAS) AF: 0.505 AC: 2422 AN: 4800

European-Finnish (FIN) AF: 0.737 AC: 7681 AN: 10422

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.675 AC: 45804 AN: 67868

Other (OTH) AF: 0.664 AC: 1394 AN: 2098

Alfa AF: 0.676 Hom.: 80854

Bravo AF: 0.678

Asia WGS AF: 0.645 AC: 2245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.41
DANN	Benign	0.74
PhyloP100		-0.84
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: rs10821936; hg19: chr10-63723577;