rs61737563

Positions:

• chr7-36406246-A-C
• chr7-36406246-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018685.5(ANLN):​c.553A>C​(p.Arg185=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 1,613,920 control chromosomes in the GnomAD database, including 7,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (530 hom., cov: 33)
  • Exomes 𝑓: 0.091 (6670 hom.)
• Consequence: ANLN NM_018685.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.06

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-36406246-A-C is Benign according to our data. Variant chr7-36406246-A-C is described in ClinVar as [Benign]. Clinvar id is 261050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANLN	NM_018685.5	c.553A>C	p.Arg185=	synonymous_variant	4/24	ENST00000265748.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANLN	ENST00000265748.7	c.553A>C	p.Arg185=	synonymous_variant	4/24	1	NM_018685.5	P2
ANLN	ENST00000396068.6	c.553A>C	p.Arg185=	synonymous_variant	4/23	1		A2
ANLN	ENST00000424865.1	c.487A>C	p.Arg163=	synonymous_variant	4/4	3
ANLN	ENST00000460598.1	n.140A>C		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11769 AN: 152168 Hom.: 530 Cov.: 33

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.000960

Gnomad SAS AF: 0.0252

Gnomad FIN AF: 0.0576

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0853

GnomAD3 exomes AF: 0.0722 AC: 18145 AN: 251392 Hom.: 836 AF XY: 0.0720 AC XY: 9789 AN XY: 135876

Gnomad AFR exome AF: 0.0495

Gnomad AMR exome AF: 0.0490

Gnomad ASJ exome AF: 0.0971

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0307

Gnomad FIN exome AF: 0.0601

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.0830

GnomAD4 exome AF: 0.0908 AC: 132776 AN: 1461634 Hom.: 6670 Cov.: 30 AF XY: 0.0895 AC XY: 65084 AN XY: 727070

Gnomad4 AFR exome AF: 0.0467

Gnomad4 AMR exome AF: 0.0506

Gnomad4 ASJ exome AF: 0.0937

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0293

Gnomad4 FIN exome AF: 0.0658

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.0853

GnomAD4 genome AF: 0.0774 AC: 11781 AN: 152286 Hom.: 530 Cov.: 33 AF XY: 0.0737 AC XY: 5485 AN XY: 74470

Gnomad4 AFR AF: 0.0514

Gnomad4 AMR AF: 0.0689

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0248

Gnomad4 FIN AF: 0.0576

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0840

Alfa AF: 0.0957 Hom.: 381

Bravo AF: 0.0768

Asia WGS AF: 0.0140 AC: 48 AN: 3478

EpiCase AF: 0.103

EpiControl AF: 0.104

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	GeneDx	Nov 29, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Mar 18, 2021	- -

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
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.5
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs61737563; hg19: chr7-36445855;