Genetic Variant ARF6:p.Leu17Leu (chr14-49893787-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001663.4(ARF6):c.51C>T(p.Leu17Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00101 in 1,614,232 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 12 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 5 hom. )

Consequence

ARF6
NM_001663.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.97

Publications

0 publications found

Variant links:

Genes affected

ARF6 (HGNC:659): (ADP ribosylation factor 6) This gene encodes a member of the human ARF gene family, which is part of the RAS superfamily. The ARF genes encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking and as activators of phospholipase D. The product of this gene is localized to the plasma membrane, and regulates vesicular trafficking, remodelling of membrane lipids, and signaling pathways that lead to actin remodeling. A pseudogene of this gene is located on chromosome 7. [provided by RefSeq, Jul 2008]

ARF6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 14-49893787-C-T is Benign according to our data. Variant chr14-49893787-C-T is described in ClinVar as Benign. ClinVar VariationId is 710032.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00559 (852/152344) while in subpopulation AFR AF = 0.0195 (809/41584). AF 95% confidence interval is 0.0183. There are 12 homozygotes in GnomAd4. There are 407 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 852 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARF6	NM_001663.4 link	c.51C>T	p.Leu17Leu	synonymous_variant	Exon 2 of 2	ENST00000298316.7	NP_001654.1	P62330

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARF6	ENST00000298316.7 link	c.51C>T	p.Leu17Leu	synonymous_variant	Exon 2 of 2	1	NM_001663.4	ENSP00000298316.5	P62330
ARF6	ENST00000693319.1 link	c.51C>T	p.Leu17Leu	synonymous_variant	Exon 1 of 1			ENSP00000510419.1	P62330
ARF6	ENST00000692608.1 link	c.-15-322C>T		intron_variant	Intron 2 of 2			ENSP00000510807.1	A0A8I5QJX7

Frequencies

GnomAD3 genomes

AF:

0.00559

AC:

851

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00140

AC:

351

AN:

251378

AF XY:

0.000986

show subpopulations

Gnomad AFR exome

AF:

0.0196

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000537

AC:

785

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000447

AC XY:

325

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0202

AC:

676

AN:

33480

American (AMR)

AF:

0.000827

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1112012

Other (OTH)

AF:

0.000960

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

100

150

200

250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00559

AC:

852

AN:

152344

Hom.:

Cov.:

AF XY:

0.00546

AC XY:

407

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0195

AC:

809

AN:

41584

American (AMR)

AF:

0.00196

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68024

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

134

178

223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00226

Hom.:

Bravo

AF:

0.00615

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over