ENST00000334211.12:c.-430T>G

Variant names:

• chr11-72722053-A-C
• rs1552224
• ENST00000334211.12:c.-430T>G

Variant summary

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

The ENST00000334211.12(ARAP1):​c.-430T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 985,342 control chromosomes in the GnomAD database, including 11,185 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 (1384 hom., cov: 32)
  • Exomes 𝑓: 0.15 (9801 hom.)
• Consequence: ARAP1 ENST00000334211.12 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700
• Publications: 215 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000334211.12. 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
	ARAP1	NM_001040118.3	MANE Select	c.509+4567T>G		intron	N/A	NP_001035207.1	Q96P48-6
	ARAP1	NM_015242.5		c.-430T>G		5_prime_UTR	Exon 1 of 33	NP_056057.2	Q96P48-4
	ARAP1	NM_001369489.1		c.-430T>G		5_prime_UTR	Exon 1 of 32	NP_001356418.1	E7EU13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAP1	ENST00000334211.12	TSL:1	c.-430T>G		5_prime_UTR	Exon 1 of 33	ENSP00000335506.8	Q96P48-4
	ARAP1	ENST00000393609.8	TSL:2 MANE Select	c.509+4567T>G		intron	N/A	ENSP00000377233.3	Q96P48-6
	ARAP1	ENST00000852596.1		c.509+4567T>G		intron	N/A	ENSP00000522655.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17747 AN: 151984 Hom.: 1388 Cov.: 32

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0822

Gnomad EAS AF: 0.0725

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.0972

GnomAD4 exome AF: 0.151 AC: 125444 AN: 833242 Hom.: 9801 Cov.: 28 AF XY: 0.152 AC XY: 58539 AN XY: 384804

African (AFR) AF: 0.0169 AC: 267 AN: 15796

American (AMR) AF: 0.0986 AC: 97 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 450 AN: 5156

East Asian (EAS) AF: 0.0590 AC: 215 AN: 3642

South Asian (SAS) AF: 0.172 AC: 2835 AN: 16464

European-Finnish (FIN) AF: 0.205 AC: 60 AN: 292

Middle Eastern (MID) AF: 0.0846 AC: 137 AN: 1620

European-Non Finnish (NFE) AF: 0.155 AC: 117965 AN: 761984

Other (OTH) AF: 0.125 AC: 3418 AN: 27304

GnomAD4 genome AF: 0.117 AC: 17743 AN: 152100 Hom.: 1384 Cov.: 32 AF XY: 0.123 AC XY: 9116 AN XY: 74364

African (AFR) AF: 0.0272 AC: 1127 AN: 41476

American (AMR) AF: 0.103 AC: 1569 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0822 AC: 285 AN: 3468

East Asian (EAS) AF: 0.0726 AC: 376 AN: 5176

South Asian (SAS) AF: 0.185 AC: 892 AN: 4826

European-Finnish (FIN) AF: 0.256 AC: 2704 AN: 10568

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10452 AN: 67978

Other (OTH) AF: 0.0976 AC: 206 AN: 2110

Alfa AF: 0.135 Hom.: 7145

Bravo AF: 0.0986

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.67
PhyloP100		-0.70
PromoterAI		0.19	Neutral
Mutation Taster		=294/6	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1552224;

hg19: chr11-72433098;