15-89904714-A-G

Variant names:

• chr15-89904714-A-G
• rs7178909
• NM_182616.4:c.302-731T>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• Publications: 19 publications found

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-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]

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARPIN	NM_182616.4	c.302-731T>C		intron_variant	Intron 3 of 5	ENST00000357484.10	NP_872422.1
ARPIN-AP3S2	NM_001199058.2	c.302-731T>C		intron_variant	Intron 3 of 9		NP_001185987.1
ARPIN	NM_001282380.2	c.14-731T>C		intron_variant	Intron 3 of 5		NP_001269309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARPIN	ENST00000357484.10	c.302-731T>C		intron_variant	Intron 3 of 5	1	NM_182616.4	ENSP00000350075.5
ARPIN-AP3S2	ENST00000398333.7	c.302-731T>C		intron_variant	Intron 3 of 9	2		ENSP00000381377.3

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61178 AN: 152004 Hom.: 12716 Cov.: 32

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.: 32 AF XY: 0.405 AC XY: 30114 AN XY: 74360

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.79
PhyloP100		0.23
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: rs7178909; hg19: chr15-90447946;