NM_032199.3:c.277-47A>C

Variant names:

• chr10-61940136-A-C
• rs7073837
• NM_032199.3:c.277-47A>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.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
• Publications: 28 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 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.277-47A>C		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.277-47A>C		intron	N/A	ENSP00000279873.7
	ARID5B	ENST00000644638.1		c.277-47A>C		intron	N/A	ENSP00000494412.1
	ARID5B	ENST00000681100.1		c.277-47A>C		intron	N/A	ENSP00000506119.1

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

GnomAD2 exomes AF: 0.578 AC: 143164 AN: 247868 AF XY: 0.568

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 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

African (AFR) AF: 0.724 AC: 23694 AN: 32720

American (AMR) AF: 0.494 AC: 21953 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 15123 AN: 25878

East Asian (EAS) AF: 0.632 AC: 24942 AN: 39484

South Asian (SAS) AF: 0.381 AC: 32468 AN: 85290

European-Finnish (FIN) AF: 0.689 AC: 36711 AN: 53246

Middle Eastern (MID) AF: 0.558 AC: 3187 AN: 5710

European-Non Finnish (NFE) AF: 0.602 AC: 651253 AN: 1081500

Other (OTH) AF: 0.588 AC: 34871 AN: 59312

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

African (AFR) AF: 0.720 AC: 29846 AN: 41450

American (AMR) AF: 0.528 AC: 8067 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2078 AN: 3470

East Asian (EAS) AF: 0.627 AC: 3236 AN: 5158

South Asian (SAS) AF: 0.391 AC: 1883 AN: 4814

European-Finnish (FIN) AF: 0.686 AC: 7228 AN: 10544

Middle Eastern (MID) AF: 0.559 AC: 162 AN: 290

European-Non Finnish (NFE) AF: 0.612 AC: 41639 AN: 67988

Other (OTH) AF: 0.604 AC: 1274 AN: 2110

Alfa AF: 0.611 Hom.: 125499

Bravo AF: 0.624

Asia WGS AF: 0.590 AC: 2052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.50
PhyloP100		-0.63
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: rs7073837; hg19: chr10-63699895;