5-141657710-T-G

Position:

• chr5-141657710-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022481.6(ARAP3):​c.3526+655A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,026 control chromosomes in the GnomAD database, including 19,392 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 0.49 (19392 hom., cov: 32)
• Consequence: ARAP3 NM_022481.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

Genes affected

ARAP3 (HGNC:24097): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 3) This gene encodes a phosphoinositide binding protein containing ARF-GAP, RHO-GAP, RAS-associating, and pleckstrin homology domains. The ARF-GAP and RHO-GAP domains cooperate in mediating rearrangements in the cell cytoskeleton and cell shape. It is a specific PtdIns(3,4,5)P3/PtdIns(3,4)P2-stimulated Arf6-GAP protein. An alternatively spliced transcript has been found for this gene, but its biological validity has not been determined. [provided by RefSeq, Sep 2015]

ARAP3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARAP3	NM_022481.6	c.3526+655A>C		intron_variant		ENST00000239440.9	NP_071926.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARAP3	ENST00000239440.9	c.3526+655A>C		intron_variant		1	NM_022481.6	ENSP00000239440.4

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74485 AN: 151908 Hom.: 19347 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.491 AC: 74588 AN: 152026 Hom.: 19392 Cov.: 32 AF XY: 0.487 AC XY: 36194 AN XY: 74302

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.444

Alfa AF: 0.442 Hom.: 10153

Bravo AF: 0.511

Asia WGS AF: 0.357 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs6895094; hg19: chr5-141037277;