chr7-36406246-A-C

Variant names:

• chr7-36406246-A-C
• rs61737563
• NM_018685.5:c.553A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018685.5(ANLN):​c.553A>C​(p.Arg185Arg) 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
• Publications: 8 publications found

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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANLN	NM_018685.5	MANE Select	c.553A>C	p.Arg185Arg	synonymous	Exon 4 of 24	NP_061155.2
	ANLN	NM_001284301.3		c.553A>C	p.Arg185Arg	synonymous	Exon 4 of 23	NP_001271230.1
	ANLN	NM_001284302.3		c.553A>C	p.Arg185Arg	synonymous	Exon 4 of 23	NP_001271231.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANLN	ENST00000265748.7	TSL:1 MANE Select	c.553A>C	p.Arg185Arg	synonymous	Exon 4 of 24	ENSP00000265748.2
	ANLN	ENST00000396068.6	TSL:1	c.553A>C	p.Arg185Arg	synonymous	Exon 4 of 23	ENSP00000379380.2
	ANLN	ENST00000424865.1	TSL:3	c.487A>C	p.Arg163Arg	synonymous	Exon 4 of 4	ENSP00000404979.1

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

GnomAD2 exomes AF: 0.0722 AC: 18145 AN: 251392 AF XY: 0.0720

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 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

African (AFR) AF: 0.0467 AC: 1564 AN: 33478

American (AMR) AF: 0.0506 AC: 2265 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0937 AC: 2448 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39696

South Asian (SAS) AF: 0.0293 AC: 2523 AN: 86252

European-Finnish (FIN) AF: 0.0658 AC: 3516 AN: 53414

Middle Eastern (MID) AF: 0.0869 AC: 501 AN: 5768

European-Non Finnish (NFE) AF: 0.103 AC: 114800 AN: 1111780

Other (OTH) AF: 0.0853 AC: 5154 AN: 60392

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

African (AFR) AF: 0.0514 AC: 2137 AN: 41576

American (AMR) AF: 0.0689 AC: 1054 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 358 AN: 3472

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5194

South Asian (SAS) AF: 0.0248 AC: 120 AN: 4832

European-Finnish (FIN) AF: 0.0576 AC: 611 AN: 10604

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7123 AN: 68004

Other (OTH) AF: 0.0840 AC: 177 AN: 2108

Alfa AF: 0.0890 Hom.: 413

Bravo AF: 0.0768

Asia WGS AF: 0.0140 AC: 48 AN: 3478

EpiCase AF: 0.103

EpiControl AF: 0.104

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Focal segmental glomerulosclerosis 8 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.5
DANN	Benign	0.66
PhyloP100		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61737563; hg19: chr7-36445855;