rs4948502

Variant names:

• chr10-62079658-T-C
• rs4948502
• NM_032199.3:c.1200-6044T>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.1200-6044T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,052 control chromosomes in the GnomAD database, including 9,237 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 0.33 (9237 hom., cov: 32)
• Consequence: ARID5B NM_032199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 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.1200-6044T>C		intron	N/A	NP_115575.1
	ARID5B	NM_001244638.2		c.471-6044T>C		intron	N/A	NP_001231567.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID5B	ENST00000279873.12	TSL:1 MANE Select	c.1200-6044T>C		intron	N/A	ENSP00000279873.7
	ARID5B	ENST00000681100.1		c.1176-6044T>C		intron	N/A	ENSP00000506119.1
	ARID5B	ENST00000309334.5	TSL:5	c.471-6044T>C		intron	N/A	ENSP00000308862.5

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50430 AN: 151934 Hom.: 9242 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.332 AC: 50419 AN: 152052 Hom.: 9237 Cov.: 32 AF XY: 0.330 AC XY: 24500 AN XY: 74306

African (AFR) AF: 0.184 AC: 7645 AN: 41490

American (AMR) AF: 0.276 AC: 4228 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1171 AN: 3472

East Asian (EAS) AF: 0.322 AC: 1659 AN: 5158

South Asian (SAS) AF: 0.384 AC: 1849 AN: 4820

European-Finnish (FIN) AF: 0.400 AC: 4220 AN: 10558

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28510 AN: 67948

Other (OTH) AF: 0.311 AC: 656 AN: 2106

Alfa AF: 0.390 Hom.: 6189

Bravo AF: 0.311

Asia WGS AF: 0.334 AC: 1163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.41
PhyloP100		-2.0
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: rs4948502; hg19: chr10-63839417;