Genetic Variant ARID5B:p.Leu210Leu (chr10-62000216-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_032199.3(ARID5B):c.628C>T(p.Leu210Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000424 in 1,613,998 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 1 hom. )

Consequence

ARID5B
NM_032199.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.87

Variant links:

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 links:

LOC124902435 (HGNC:):

LOC124902435 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 10-62000216-C-T is Benign according to our data. Variant chr10-62000216-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3040475.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 70 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID5B	NM_032199.3 link	c.628C>T	p.Leu210Leu	synonymous_variant	Exon 4 of 10	ENST00000279873.12	NP_115575.1	Q14865-1
LOC124902435	XR_007062155.1 link	n.104+131G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARID5B	ENST00000279873.12 link	c.628C>T	p.Leu210Leu	synonymous_variant	Exon 4 of 10	1	NM_032199.3	ENSP00000279873.7	Q14865-1
ARID5B	ENST00000644638.1 link	c.628C>T	p.Leu210Leu	synonymous_variant	Exon 4 of 5			ENSP00000494412.1	A0A2R8Y5F2
ARID5B	ENST00000681100.1 link	c.628C>T	p.Leu210Leu	synonymous_variant	Exon 4 of 10			ENSP00000506119.1	A0A7P0TAD2

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000526

AC:

132

AN:

251106

Hom.:

AF XY:

0.000457

AC XY:

AN XY:

135688

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00337

Gnomad NFE exome

AF:

0.000405

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.000420

AC:

614

AN:

1461726

Hom.:

Cov.:

AF XY:

0.000397

AC XY:

289

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00292

Gnomad4 NFE exome

AF:

0.000367

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000460

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000541

Hom.:

Bravo

AF:

0.000238

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ARID5B-related disorder

Benign:1

Mar 29, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.95

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over