Genetic Variant NM_182616.4:c.302-731T>C (chr15-89904714-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_182616.4(ARPIN):c.302-731T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,122 control chromosomes in the GnomAD database, including 12,725 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 0.40 ( 12725 hom., cov: 32)

Consequence

ARPIN
NM_182616.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.235

Publications

19 publications found

Variant links:

Genes affected

ARPIN (HGNC:28782): (actin related protein 2/3 complex inhibitor) Involved in directional locomotion; negative regulation of cell migration; and negative regulation of cellular component organization. Predicted to be located in lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

ARPIN links:

ARPIN-AP3S2 (HGNC:38824): (ARPIN-AP3S2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring C15orf38 (chromosome 15 open reading frame 38) and AP3S2 (adaptor-related protein complex 3, sigma 2 subunit) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

ARPIN-AP3S2 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182616.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARPIN	NM_182616.4	MANE Select	c.302-731T>C	intron	N/A	NP_872422.1	Q7Z6K5-1
ARPIN-AP3S2	NM_001199058.2		c.302-731T>C	intron	N/A	NP_001185987.1
ARPIN	NM_001282380.2		c.14-731T>C	intron	N/A	NP_001269309.1	H0YMP5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARPIN	ENST00000357484.10	TSL:1 MANE Select	c.302-731T>C	intron	N/A	ENSP00000350075.5	Q7Z6K5-1
ARPIN-AP3S2	ENST00000398333.7	TSL:2	c.302-731T>C	intron	N/A	ENSP00000381377.3
ARPIN	ENST00000969751.1		c.302-842T>C	intron	N/A	ENSP00000639810.1

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

61178

AN:

152004

Hom.:

12716

Cov.:

show subpopulations

Gnomad AFR

AF:

0.389

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.397

Gnomad EAS

AF:

0.632

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.330

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.431

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.402

AC:

61212

AN:

152122

Hom.:

12725

Cov.:

AF XY:

0.405

AC XY:

30114

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.388

AC:

16100

AN:

41478

American (AMR)

AF:

0.544

AC:

8314

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

1376

AN:

3470

East Asian (EAS)

AF:

0.633

AC:

3269

AN:

5166

South Asian (SAS)

AF:

0.331

AC:

1601

AN:

4832

European-Finnish (FIN)

AF:

0.330

AC:

3489

AN:

10580

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.378

AC:

25685

AN:

67988

Other (OTH)

AF:

0.434

AC:

918

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1872

3744

5616

7488

9360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.395

Hom.:

37553

Bravo

AF:

0.423

Asia WGS

AF:

0.460

AC:

1601

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.5

(source)

DANN

Benign

0.79

PhyloP100

0.23

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over