rs1612554

Positions:

• chr4-35967126-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The XR_925191.3(LOC105374397):​n.306+697G>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 152,084 control chromosomes in the GnomAD database, including 681 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 0.086 (681 hom., cov: 32)
• Consequence: LOC105374397 XR_925191.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173

Genes affected

ARAP2 (HGNC:16924): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2) The protein encoded by this gene contains ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology domains. The protein is a phosphatidylinositol (3,4,5)-trisphosphate-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RHO-GAP domain and does not have RHO-GAP activity. The protein associates with focal adhesions and functions downstream of RhoA to regulate focal adhesion dynamics. [provided by RefSeq, Sep 2008]

LOC105374397 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105374397	XR_925191.3	n.306+697G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARAP2	ENST00000503225.5	n.1741+697G>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0855 AC: 12992 AN: 151966 Hom.: 669 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.0561

Gnomad SAS AF: 0.0502

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0914

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

GnomAD4 genome AF: 0.0857 AC: 13036 AN: 152084 Hom.: 681 Cov.: 32 AF XY: 0.0836 AC XY: 6220 AN XY: 74366

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.0554

Gnomad4 SAS AF: 0.0496

Gnomad4 FIN AF: 0.0344

Gnomad4 NFE AF: 0.0766

Gnomad4 OTH AF: 0.0971

Alfa AF: 0.0789 Hom.: 241

Bravo AF: 0.0899

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	11
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1612554; hg19: chr4-35968748;