5-141657710-T-G

Variant names:

• chr5-141657710-T-G
• rs6895094
• NM_022481.6:c.3526+655A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022481.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAP3	NM_022481.6	MANE Select	c.3526+655A>C		intron	N/A	NP_071926.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAP3	ENST00000239440.9	TSL:1 MANE Select	c.3526+655A>C		intron	N/A	ENSP00000239440.4	Q8WWN8-1
	ARAP3	ENST00000955414.1		c.3526+655A>C		intron	N/A	ENSP00000625473.1
	ARAP3	ENST00000925545.1		c.3466+655A>C		intron	N/A	ENSP00000595604.1

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

African (AFR) AF: 0.682 AC: 28272 AN: 41474

American (AMR) AF: 0.520 AC: 7948 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1198 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2075 AN: 5160

South Asian (SAS) AF: 0.316 AC: 1519 AN: 4812

European-Finnish (FIN) AF: 0.424 AC: 4471 AN: 10556

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27724 AN: 67956

Other (OTH) AF: 0.444 AC: 936 AN: 2110

Alfa AF: 0.457 Hom.: 15214

Bravo AF: 0.511

Asia WGS AF: 0.357 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.48
PhyloP100		-1.1
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: rs6895094; hg19: chr5-141037277;