Variant 7-36406247-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018685.5(ANLN):c.554G>A(p.Arg185Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 1,613,538 control chromosomes in the GnomAD database, including 328,974 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27209 hom., cov: 33)

Exomes 𝑓: 0.64 ( 301765 hom. )

Consequence

ANLN
NM_018685.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.49

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.575349E-7).

BP6

Variant 7-36406247-G-A is Benign according to our data. Variant chr7-36406247-G-A is described in ClinVar as [Benign]. Clinvar id is 261051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANLN	NM_018685.5 linkuse as main transcript	c.554G>A	p.Arg185Lys	missense_variant	4/24	ENST00000265748.7	NP_061155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANLN	ENST00000265748.7 linkuse as main transcript	c.554G>A	p.Arg185Lys	missense_variant	4/24	1	NM_018685.5	ENSP00000265748	P2	Q9NQW6-1
ANLN	ENST00000396068.6 linkuse as main transcript	c.554G>A	p.Arg185Lys	missense_variant	4/23	1		ENSP00000379380	A2	Q9NQW6-2
ANLN	ENST00000424865.1 linkuse as main transcript	c.488G>A	p.Arg163Lys	missense_variant	4/4	3		ENSP00000404979
ANLN	ENST00000460598.1 linkuse as main transcript	n.141G>A		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89711

AN:

151924

Hom.:

27182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.447

Gnomad AMI

AF:

0.811

Gnomad AMR

AF:

0.595

Gnomad ASJ

AF:

0.697

Gnomad EAS

AF:

0.724

Gnomad SAS

AF:

0.756

Gnomad FIN

AF:

0.689

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.631

Gnomad OTH

AF:

0.589

GnomAD3 exomes

AF:

0.654

AC:

164409

AN:

251334

Hom.:

54444

AF XY:

0.660

AC XY:

89700

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.446

Gnomad AMR exome

AF:

0.669

Gnomad ASJ exome

AF:

0.691

Gnomad EAS exome

AF:

0.727

Gnomad SAS exome

AF:

0.751

Gnomad FIN exome

AF:

0.691

Gnomad NFE exome

AF:

0.632

Gnomad OTH exome

AF:

0.648

GnomAD4 exome

AF:

0.641

AC:

936326

AN:

1461496

Hom.:

301765

Cov.:

AF XY:

0.644

AC XY:

468078

AN XY:

726984

show subpopulations

Gnomad4 AFR exome

AF:

0.439

Gnomad4 AMR exome

AF:

0.659

Gnomad4 ASJ exome

AF:

0.696

Gnomad4 EAS exome

AF:

0.746

Gnomad4 SAS exome

AF:

0.743

Gnomad4 FIN exome

AF:

0.684

Gnomad4 NFE exome

AF:

0.631

Gnomad4 OTH exome

AF:

0.639

GnomAD4 genome

AF:

0.591

AC:

89790

AN:

152042

Hom.:

27209

Cov.:

AF XY:

0.597

AC XY:

44384

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.447

Gnomad4 AMR

AF:

0.596

Gnomad4 ASJ

AF:

0.697

Gnomad4 EAS

AF:

0.723

Gnomad4 SAS

AF:

0.755

Gnomad4 FIN

AF:

0.689

Gnomad4 NFE

AF:

0.631

Gnomad4 OTH

AF:

0.591

Alfa

AF:

0.628

Hom.:

45823

Bravo

AF:

0.574

TwinsUK

AF:

0.623

AC:

2310

ALSPAC

AF:

0.628

AC:

2421

ESP6500AA

AF:

0.433

AC:

1906

ESP6500EA

AF:

0.594

AC:

5105

ExAC

AF:

0.650

AC:

78914

Asia WGS

AF:

0.725

AC:

2517

AN:

3478

EpiCase

AF:

0.624

EpiControl

AF:

0.619

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Focal segmental glomerulosclerosis 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.9

DANN

Benign

0.64

DEOGEN2

Benign

0.027

T;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.098

T;T;T

MetaRNN

Benign

8.6e-7

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.1

N;N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

1.1

N;N;N

REVEL

Benign

0.081

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.028

MPC

0.13

ClinPred

0.0022

GERP RS

3.6

Varity_R

0.041

gMVP

0.12

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over