rs4509706

Variant names:

• chr10-61901581-T-C
• rs4509706
• ENST00000827147.1:n.91A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000827147.1(ENSG00000307565):​n.91A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 920,958 control chromosomes in the GnomAD database, including 4,628 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 0.084 (607 hom., cov: 32)
  • Exomes 𝑓: 0.099 (4021 hom.)
• Consequence: ENSG00000307565 ENST00000827147.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.664
• Publications: 6 publications found

Genes affected

ENSG00000307565 (HGNC:):

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=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID5B	NM_032199.3	c.-129T>C		upstream_gene_variant		ENST00000279873.12	NP_115575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID5B	ENST00000279873.12	c.-129T>C		upstream_gene_variant		1	NM_032199.3	ENSP00000279873.7
ARID5B	ENST00000644638.1	c.-129T>C		upstream_gene_variant				ENSP00000494412.1

Frequencies

GnomAD3 genomes AF: 0.0845 AC: 12853 AN: 152122 Hom.: 607 Cov.: 32

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0903

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0970

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.0827

GnomAD4 exome AF: 0.0992 AC: 76251 AN: 768720 Hom.: 4021 Cov.: 10 AF XY: 0.0985 AC XY: 39651 AN XY: 402618

African (AFR) AF: 0.0491 AC: 993 AN: 20232

American (AMR) AF: 0.135 AC: 5545 AN: 41130

Ashkenazi Jewish (ASJ) AF: 0.0811 AC: 1667 AN: 20566

East Asian (EAS) AF: 0.121 AC: 4346 AN: 35992

South Asian (SAS) AF: 0.0932 AC: 6449 AN: 69172

European-Finnish (FIN) AF: 0.0836 AC: 4291 AN: 51302

Middle Eastern (MID) AF: 0.0552 AC: 240 AN: 4348

European-Non Finnish (NFE) AF: 0.100 AC: 49106 AN: 488620

Other (OTH) AF: 0.0967 AC: 3614 AN: 37358

GnomAD4 genome AF: 0.0845 AC: 12857 AN: 152238 Hom.: 607 Cov.: 32 AF XY: 0.0822 AC XY: 6122 AN XY: 74432

African (AFR) AF: 0.0496 AC: 2062 AN: 41546

American (AMR) AF: 0.105 AC: 1605 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0903 AC: 313 AN: 3468

East Asian (EAS) AF: 0.130 AC: 675 AN: 5184

South Asian (SAS) AF: 0.0968 AC: 467 AN: 4822

European-Finnish (FIN) AF: 0.0734 AC: 777 AN: 10584

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0991 AC: 6741 AN: 68018

Other (OTH) AF: 0.0818 AC: 173 AN: 2114

Alfa AF: 0.0892 Hom.: 885

Bravo AF: 0.0867

Asia WGS AF: 0.108 AC: 377 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 17, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29292192) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		0.66
PromoterAI		-0.022	Neutral
Mutation Taster		=300/0	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: rs4509706; hg19: chr10-63661340;