rs3886999

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139321.3(ATRN):c.3455G>A(p.Arg1152Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0477 in 1,613,122 control chromosomes in the GnomAD database, including 2,117 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 148 hom., cov: 32)

Exomes 𝑓: 0.049 ( 1969 hom. )

Consequence

ATRN
NM_139321.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.79

Publications

18 publications found

Variant links:

Genes affected

ATRN (HGNC:885): (attractin) This gene encodes both membrane-bound and secreted protein isoforms. A membrane-bound isoform exhibits sequence similarity with the mouse mahogany protein, a receptor involved in controlling obesity. A secreted isoform is involved in the initial immune cell clustering during inflammatory responses that may regulate the chemotactic activity of chemokines. [provided by RefSeq, Apr 2016]

ATRN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049655437).

BP6

Variant 20-3596415-G-A is Benign according to our data. Variant chr20-3596415-G-A is described in ClinVar as Benign. ClinVar VariationId is 1167767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATRN	NM_139321.3 link	c.3455G>A	p.Arg1152Lys	missense_variant	Exon 21 of 29	ENST00000262919.10	NP_647537.1	O75882-1
ATRN	NM_001323332.2 link	c.3455G>A	p.Arg1152Lys	missense_variant	Exon 21 of 26		NP_001310261.1	O75882
ATRN	NM_139322.4 link	c.3455G>A	p.Arg1152Lys	missense_variant	Exon 21 of 25		NP_647538.1	O75882-2B4DZ36
ATRN	NM_001207047.3 link	c.3107G>A	p.Arg1036Lys	missense_variant	Exon 21 of 25		NP_001193976.1	O75882B4DZ36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATRN	ENST00000262919.10 link	c.3455G>A	p.Arg1152Lys	missense_variant	Exon 21 of 29	5	NM_139321.3	ENSP00000262919.5		O75882-1
ATRN	ENST00000446916.2 link	c.3455G>A	p.Arg1152Lys	missense_variant	Exon 21 of 25	1		ENSP00000416587.2		O75882-2

Frequencies

GnomAD3 genomes

AF:

0.0382

AC:

5812

AN:

152184

Hom.:

148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00934

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.0406

Gnomad ASJ

AF:

0.0274

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0132

Gnomad FIN

AF:

0.0610

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0561

Gnomad OTH

AF:

0.0406

GnomAD2 exomes

AF:

0.0394

AC:

9883

AN:

251052

AF XY:

0.0397

show subpopulations

Gnomad AFR exome

AF:

0.00831

Gnomad AMR exome

AF:

0.0285

Gnomad ASJ exome

AF:

0.0333

Gnomad EAS exome

AF:

0.000707

Gnomad FIN exome

AF:

0.0683

Gnomad NFE exome

AF:

0.0557

Gnomad OTH exome

AF:

0.0443

GnomAD4 exome

AF:

0.0487

AC:

71191

AN:

1460820

Hom.:

1969

Cov.:

AF XY:

0.0479

AC XY:

34843

AN XY:

726770

show subpopulations

African (AFR)

AF:

0.00822

AC:

275

AN:

33470

American (AMR)

AF:

0.0295

AC:

1320

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0335

AC:

876

AN:

26114

East Asian (EAS)

AF:

0.00527

AC:

209

AN:

39668

South Asian (SAS)

AF:

0.0113

AC:

971

AN:

86234

European-Finnish (FIN)

AF:

0.0687

AC:

3666

AN:

53390

Middle Eastern (MID)

AF:

0.0203

AC:

117

AN:

5764

European-Non Finnish (NFE)

AF:

0.0551

AC:

61197

AN:

1111108

Other (OTH)

AF:

0.0424

AC:

2560

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

3211

6422

9633

12844

16055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2186

4372

6558

8744

10930

<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:

0.0382

AC:

5812

AN:

152302

Hom.:

148

Cov.:

AF XY:

0.0379

AC XY:

2821

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00931

AC:

387

AN:

41568

American (AMR)

AF:

0.0406

AC:

621

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0274

AC:

AN:

3472

East Asian (EAS)

AF:

0.00173

AC:

AN:

5194

South Asian (SAS)

AF:

0.0135

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0610

AC:

647

AN:

10604

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0561

AC:

3817

AN:

68014

Other (OTH)

AF:

0.0402

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

284

567

851

1134

1418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0499

Hom.:

693

Bravo

AF:

0.0354

TwinsUK

AF:

0.0545

AC:

202

ALSPAC

AF:

0.0612

AC:

236

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.0562

AC:

483

ExAC

AF:

0.0389

AC:

4718

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0553

EpiControl

AF:

0.0584

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ATRN-related disorder

Benign:1

Jul 29, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.061

T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.39

T;T

MetaRNN

Benign

0.0050

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.28

N;N

PhyloP100

5.8

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.23

N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T

Sift4G

Benign

0.87

T;T

Polyphen

0.0

B;B

Vest4

0.053

MPC

0.53

ClinPred

0.029

GERP RS

6.0

Varity_R

0.079

gMVP

0.22

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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