rs197367

Positions:

• chr7-36406247-G-A
• chr7-36406247-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.49

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]

ACMG classification

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	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	c.554G>A	p.Arg185Lys	missense_variant	4/24	1	NM_018685.5	ENSP00000265748	P2
ANLN	ENST00000396068.6	c.554G>A	p.Arg185Lys	missense_variant	4/23	1		ENSP00000379380	A2
ANLN	ENST00000424865.1	c.488G>A	p.Arg163Lys	missense_variant	4/4	3		ENSP00000404979
ANLN	ENST00000460598.1	n.141G>A		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89711 AN: 151924 Hom.: 27182 Cov.: 33

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

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.: 52 AF XY: 0.644 AC XY: 468078 AN XY: 726984

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.: 33 AF XY: 0.597 AC XY: 44384 AN XY: 74348

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

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	T
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	N
LIST_S2	Benign	0.098	T;T;T
MetaRNN	Benign	8.6e-7	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.1	N;N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.34	T
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	T
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

Other links and lift over

dbSNP: rs197367; hg19: chr7-36445856; COSMIC: COSV56076351; COSMIC: COSV56076351;