Genetic Variant ANLN:p.Arg13His (chr7-36396285-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PP3BP4_StrongBP6_ModerateBS2

The NM_018685.5(ANLN):c.38G>A(p.Arg13His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,605,254 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R13C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

ANLN
NM_018685.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.21

Publications

3 publications found

Variant links:

Genes affected

ANLN (HGNC:14082): (anillin, actin binding protein) This gene encodes an actin-binding protein that plays a role in cell growth and migration, and in cytokinesis. The encoded protein is thought to regulate actin cytoskeletal dynamics in podocytes, components of the glomerulus. Mutations in this gene are associated with focal segmental glomerulosclerosis 8. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

ANLN Gene-Disease associations (from GenCC):

focal segmental glomerulosclerosis 8
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ANLN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, Cadd, Dann, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PrimateAI [when BayesDel_addAF, BayesDel_noAF, max_spliceai, M_CAP, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.051848143).

BP6

Variant 7-36396285-G-A is Benign according to our data. Variant chr7-36396285-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2897844.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 45 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018685.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANLN	NM_018685.5	MANE Select	c.38G>A	p.Arg13His	missense	Exon 2 of 24	NP_061155.2
ANLN	NM_001284301.3		c.38G>A	p.Arg13His	missense	Exon 2 of 23	NP_001271230.1	Q9NQW6-2
ANLN	NM_001284302.3		c.38G>A	p.Arg13His	missense	Exon 2 of 23	NP_001271231.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANLN	ENST00000265748.7	TSL:1 MANE Select	c.38G>A	p.Arg13His	missense	Exon 2 of 24	ENSP00000265748.2	Q9NQW6-1
ANLN	ENST00000396068.6	TSL:1	c.38G>A	p.Arg13His	missense	Exon 2 of 23	ENSP00000379380.2	Q9NQW6-2
ANLN	ENST00000424865.1	TSL:3	c.-29G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000404979.1	C9JJT6

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000341

AC:

AN:

249624

AF XY:

0.000304

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad FIN exome

AF:

0.00328

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.000154

AC:

224

AN:

1452994

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

118

AN XY:

722616

show subpopulations

African (AFR)

AF:

0.0000600

AC:

AN:

33308

American (AMR)

AF:

0.0000226

AC:

AN:

44272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25840

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39536

South Asian (SAS)

AF:

0.0000937

AC:

AN:

85374

European-Finnish (FIN)

AF:

0.00305

AC:

162

AN:

53198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.0000335

AC:

AN:

1105824

Other (OTH)

AF:

0.000200

AC:

AN:

59908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000296

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41544

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00349

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000540

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.000239

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.031

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

2.9

PhyloP100

8.2

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.76

MVP

0.69

MPC

0.65

ClinPred

0.16

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.63

gMVP

0.30

Mutation Taster

=60/40

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over