11-72721940-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015242.5(ARAP1):​c.-317C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARAP1 NM_015242.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 102 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015242.5. 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+4680C>A		intron	N/A	NP_001035207.1	Q96P48-6
	ARAP1	NM_015242.5		c.-317C>A		5_prime_UTR	Exon 1 of 33	NP_056057.2	Q96P48-4
	ARAP1	NM_001369489.1		c.-317C>A		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.-317C>A		5_prime_UTR	Exon 1 of 33	ENSP00000335506.8	Q96P48-4
	ARAP1	ENST00000426523.5	TSL:1	c.-317C>A		5_prime_UTR	Exon 1 of 32	ENSP00000392264.1	E7EU13
	ARAP1	ENST00000429686.5	TSL:1	c.-317C>A		5_prime_UTR	Exon 1 of 31	ENSP00000403127.1	Q96P48-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 834196 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 385240

African (AFR) AF: 0.00 AC: 0 AN: 15804

American (AMR) AF: 0.00 AC: 0 AN: 994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5176

East Asian (EAS) AF: 0.00 AC: 0 AN: 3766

South Asian (SAS) AF: 0.00 AC: 0 AN: 16474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 762624

Other (OTH) AF: 0.00 AC: 0 AN: 27348

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 6218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.52
PhyloP100		-1.1
PromoterAI		0.019	Neutral

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: rs11603334;

hg19: chr11-72432985;