chr10-61959980-C-T

Variant names:

• chr10-61959980-C-T
• rs4948492
• NM_032199.3:c.502+19572C>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+19572C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 151,974 control chromosomes in the GnomAD database, including 36,460 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 (36460 hom., cov: 31)
• Consequence: ARID5B NM_032199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 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.502+19572C>T		intron	N/A	NP_115575.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID5B	ENST00000279873.12	TSL:1 MANE Select	c.502+19572C>T		intron	N/A	ENSP00000279873.7
	ARID5B	ENST00000644638.1		c.502+19572C>T		intron	N/A	ENSP00000494412.1
	ARID5B	ENST00000681100.1		c.502+19572C>T		intron	N/A	ENSP00000506119.1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104543 AN: 151856 Hom.: 36415 Cov.: 31

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.689 AC: 104641 AN: 151974 Hom.: 36460 Cov.: 31 AF XY: 0.685 AC XY: 50878 AN XY: 74268

African (AFR) AF: 0.774 AC: 32083 AN: 41438

American (AMR) AF: 0.559 AC: 8528 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2368 AN: 3470

East Asian (EAS) AF: 0.638 AC: 3281 AN: 5144

South Asian (SAS) AF: 0.502 AC: 2420 AN: 4824

European-Finnish (FIN) AF: 0.739 AC: 7803 AN: 10558

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45932 AN: 67966

Other (OTH) AF: 0.663 AC: 1397 AN: 2108

Alfa AF: 0.709 Hom.: 4996

Bravo AF: 0.678

Asia WGS AF: 0.644 AC: 2242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.44
PhyloP100		0.14
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: rs4948492; hg19: chr10-63719739;