Genetic Variant NM_012106.4:c.207+530C>T (chr16-57249173-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012106.4(ARL2BP):c.207+530C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 153,016 control chromosomes in the GnomAD database, including 6,712 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 0.27 ( 6668 hom., cov: 32)

Exomes 𝑓: 0.29 ( 44 hom. )

Consequence

ARL2BP
NM_012106.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.952

Variant links:

Genes affected

ARL2BP (HGNC:17146): (ADP ribosylation factor like GTPase 2 binding protein) ADP-ribosylation factor (ARF)-like proteins (ARLs) comprise a functionally distinct group of the ARF family of RAS-related GTPases. The protein encoded by this gene binds to ARL2.GTP with high affinity but does not interact with ARL2.GDP, activated ARF, or RHO proteins. The lack of detectable membrane association of this protein or ARL2 upon activation of ARL2 is suggestive of actions distinct from those of the ARFs. This protein is considered to be the first ARL2-specific effector identified, due to its interaction with ARL2.GTP but lack of ARL2 GTPase-activating protein activity. [provided by RefSeq, Jul 2008]

ARL2BP links:

PLLP (HGNC:18553): (plasmolipin) Predicted to be a structural constituent of myelin sheath. Predicted to be involved in myelination. Predicted to be located in compact myelin and membrane raft. Predicted to be integral component of membrane. Biomarker of schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

PLLP links:

LOC124903697 (HGNC:):

LOC124903697 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ARL2BP	NM_012106.4 link	c.207+530C>T	intron_variant	Intron 3 of 5	ENST00000219204.8	NP_036238.1	Q9Y2Y0-1A0A024R6U9
ARL2BP	XM_047433883.1 link	c.111+530C>T	intron_variant	Intron 3 of 5		XP_047289839.1
LOC124903697	XR_007065082.1 link	n.888G>A	non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL2BP	ENST00000219204.8 link	c.207+530C>T		intron_variant	Intron 3 of 5	1	NM_012106.4	ENSP00000219204.3		Q9Y2Y0-1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

41028

AN:

151958

Hom.:

6669

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0870

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.392

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.403

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.288

GnomAD4 exome

AF:

0.293

AC:

275

AN:

938

Hom.:

Cov.:

AF XY:

0.297

AC XY:

139

AN XY:

468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.286

AC:

AN:

South Asian (SAS)

AF:

0.0714

AC:

AN:

European-Finnish (FIN)

AF:

0.400

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.315

AC:

234

AN:

744

Other (OTH)

AF:

0.273

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.270

AC:

41029

AN:

152078

Hom.:

6668

Cov.:

AF XY:

0.271

AC XY:

20154

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0868

AC:

3601

AN:

41494

American (AMR)

AF:

0.309

AC:

4728

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

1050

AN:

3472

East Asian (EAS)

AF:

0.392

AC:

2026

AN:

5166

South Asian (SAS)

AF:

0.164

AC:

792

AN:

4822

European-Finnish (FIN)

AF:

0.403

AC:

4248

AN:

10552

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.348

AC:

23641

AN:

67974

Other (OTH)

AF:

0.287

AC:

607

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1441

2883

4324

5766

7207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.311

Hom.:

4541

Bravo

AF:

0.260

Asia WGS

AF:

0.314

AC:

1090

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

2.4

(source)

DANN

Benign

0.66

PhyloP100

-0.95

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_012106.4:c.207+530C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over