10-61925395-C-T

Variant names:

• chr10-61925395-C-T
• rs4948488
• NM_032199.3:c.277-14788C>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.277-14788C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 151,878 control chromosomes in the GnomAD database, including 45,819 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 0.77 (45819 hom., cov: 30)
• Consequence: ARID5B NM_032199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 12 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=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.826 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID5B	NM_032199.3	MANE Select	c.277-14788C>T		intron	N/A	NP_115575.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID5B	ENST00000279873.12	TSL:1 MANE Select	c.277-14788C>T		intron	N/A	ENSP00000279873.7
	ARID5B	ENST00000644638.1		c.277-14788C>T		intron	N/A	ENSP00000494412.1
	ARID5B	ENST00000681100.1		c.277-14788C>T		intron	N/A	ENSP00000506119.1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117461 AN: 151760 Hom.: 45804 Cov.: 30

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.774 AC: 117519 AN: 151878 Hom.: 45819 Cov.: 30 AF XY: 0.771 AC XY: 57200 AN XY: 74192

African (AFR) AF: 0.722 AC: 29893 AN: 41384

American (AMR) AF: 0.666 AC: 10161 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2883 AN: 3468

East Asian (EAS) AF: 0.601 AC: 3093 AN: 5144

South Asian (SAS) AF: 0.757 AC: 3649 AN: 4818

European-Finnish (FIN) AF: 0.823 AC: 8671 AN: 10534

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56532 AN: 67964

Other (OTH) AF: 0.756 AC: 1595 AN: 2110

Alfa AF: 0.803 Hom.: 84952

Bravo AF: 0.757

Asia WGS AF: 0.724 AC: 2516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.2
DANN	Benign	0.71
PhyloP100		-0.24
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: rs4948488; hg19: chr10-63685154;