ENST00000334211.12:c.-317C>T

Variant names:

• chr11-72721940-G-A
• rs11603334
• ENST00000334211.12:c.-317C>T

Variant summary

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

The ENST00000334211.12(ARAP1):​c.-317C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 986,418 control chromosomes in the GnomAD database, including 11,210 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 0.12 (1404 hom., cov: 32)
  • Exomes 𝑓: 0.15 (9806 hom.)
• Consequence: ARAP1 ENST00000334211.12 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

Genes affected

ARAP1 (HGNC:16925): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1) The protein encoded by this gene contains SAM, ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology (PH) domains. In vitro, this protein displays RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent ARF-GAP activity. The encoded protein associates with the Golgi, and the ARF-GAP activity mediates changes in the Golgi and the formation of filopodia. It is thought to regulate the cell-specific trafficking of a receptor protein involved in apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARAP1	NM_001040118.3	c.509+4680C>T		intron_variant	Intron 3 of 34	ENST00000393609.8	NP_001035207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARAP1	ENST00000393609.8	c.509+4680C>T		intron_variant	Intron 3 of 34	2	NM_001040118.3	ENSP00000377233.3

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18383 AN: 152104 Hom.: 1408 Cov.: 32

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0822

Gnomad EAS AF: 0.0727

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.0980

GnomAD4 exome AF: 0.151 AC: 125813 AN: 834196 Hom.: 9806 Cov.: 28 AF XY: 0.152 AC XY: 58676 AN XY: 385240

Gnomad4 AFR exome AF: 0.0349

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.0877

Gnomad4 EAS exome AF: 0.0574

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.121 AC: 18380 AN: 152222 Hom.: 1404 Cov.: 32 AF XY: 0.127 AC XY: 9419 AN XY: 74412

Gnomad4 AFR AF: 0.0426

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0822

Gnomad4 EAS AF: 0.0728

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.0984

Alfa AF: 0.135 Hom.: 2916

Bravo AF: 0.104

Asia WGS AF: 0.123 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.20
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11603334; hg19: chr11-72432985; COSMIC: COSV61993542;