NM_032199.3:c.734-5030T>C

Variant names:

• chr10-62045858-T-C
• rs4948496
• NM_032199.3:c.734-5030T>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.734-5030T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,106 control chromosomes in the GnomAD database, including 23,966 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 0.55 (23966 hom., cov: 32)
• Consequence: ARID5B NM_032199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220
• Publications: 44 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID5B	NM_032199.3	c.734-5030T>C		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	ENST00000279873.12	c.734-5030T>C		intron_variant	Intron 4 of 9	1	NM_032199.3	ENSP00000279873.7
ARID5B	ENST00000681100.1	c.734-5030T>C		intron_variant	Intron 4 of 9			ENSP00000506119.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84000 AN: 151988 Hom.: 23908 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.553 AC: 84127 AN: 152106 Hom.: 23966 Cov.: 32 AF XY: 0.563 AC XY: 41835 AN XY: 74354

African (AFR) AF: 0.657 AC: 27278 AN: 41496

American (AMR) AF: 0.616 AC: 9408 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2076 AN: 3472

East Asian (EAS) AF: 0.643 AC: 3330 AN: 5180

South Asian (SAS) AF: 0.608 AC: 2932 AN: 4820

European-Finnish (FIN) AF: 0.576 AC: 6083 AN: 10564

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31258 AN: 67972

Other (OTH) AF: 0.572 AC: 1208 AN: 2112

Alfa AF: 0.497 Hom.: 61186

Bravo AF: 0.562

Asia WGS AF: 0.665 AC: 2312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.25
PhyloP100		0.22
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: rs4948496; hg19: chr10-63805617;