10-61940136-A-C

Position:

• chr10-61940136-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032199.3(ARID5B):​c.277-47A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 1,579,632 control chromosomes in the GnomAD database, including 283,708 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 0.63 (30714 hom., cov: 31)
  • Exomes 𝑓: 0.59 (252994 hom.)
• Consequence: ARID5B NM_032199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID5B	NM_032199.3	c.277-47A>C		intron_variant		ENST00000279873.12	NP_115575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID5B	ENST00000279873.12	c.277-47A>C		intron_variant		1	NM_032199.3	ENSP00000279873	P3
ARID5B	ENST00000644638.1	c.277-47A>C		intron_variant				ENSP00000494412
ARID5B	ENST00000681100.1	c.277-47A>C		intron_variant				ENSP00000506119

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95906 AN: 151910 Hom.: 30674 Cov.: 31

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.600

GnomAD3 exomes AF: 0.578 AC: 143164 AN: 247868 Hom.: 42429 AF XY: 0.568 AC XY: 76032 AN XY: 133970

Gnomad AFR exome AF: 0.722

Gnomad AMR exome AF: 0.495

Gnomad ASJ exome AF: 0.579

Gnomad EAS exome AF: 0.612

Gnomad SAS exome AF: 0.380

Gnomad FIN exome AF: 0.684

Gnomad NFE exome AF: 0.609

Gnomad OTH exome AF: 0.598

GnomAD4 exome AF: 0.591 AC: 844202 AN: 1427604 Hom.: 252994 Cov.: 24 AF XY: 0.585 AC XY: 416436 AN XY: 711894

Gnomad4 AFR exome AF: 0.724

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.584

Gnomad4 EAS exome AF: 0.632

Gnomad4 SAS exome AF: 0.381

Gnomad4 FIN exome AF: 0.689

Gnomad4 NFE exome AF: 0.602

Gnomad4 OTH exome AF: 0.588

GnomAD4 genome AF: 0.631 AC: 95997 AN: 152028 Hom.: 30714 Cov.: 31 AF XY: 0.628 AC XY: 46645 AN XY: 74288

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.604

Alfa AF: 0.604 Hom.: 59735

Bravo AF: 0.624

Asia WGS AF: 0.590 AC: 2052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs7073837; hg19: chr10-63699895;