rs3815484

Variant names:

• chr7-36427046-C-A
• rs3815484
• NM_018685.5:c.2883+18C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018685.5(ANLN):​c.2883+18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,512,408 control chromosomes in the GnomAD database, including 11,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (941 hom., cov: 31)
  • Exomes 𝑓: 0.12 (10954 hom.)
• Consequence: ANLN NM_018685.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.503
• Publications: 4 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-36427046-C-A is Benign according to our data. Variant chr7-36427046-C-A is described in ClinVar as Benign. ClinVar VariationId is 261049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANLN	NM_018685.5	MANE Select	c.2883+18C>A		intron	N/A	NP_061155.2
	ANLN	NM_001284301.3		c.2772+18C>A		intron	N/A	NP_001271230.1	Q9NQW6-2
	ANLN	NM_001284302.3		c.2769+18C>A		intron	N/A	NP_001271231.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANLN	ENST00000265748.7	TSL:1 MANE Select	c.2883+18C>A		intron	N/A	ENSP00000265748.2	Q9NQW6-1
	ANLN	ENST00000396068.6	TSL:1	c.2772+18C>A		intron	N/A	ENSP00000379380.2	Q9NQW6-2
	ANLN	ENST00000918505.1		c.2883+18C>A		intron	N/A	ENSP00000588564.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15501 AN: 151772 Hom.: 944 Cov.: 31

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.0798

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.125 AC: 27850 AN: 222756 AF XY: 0.128

Gnomad AFR exome AF: 0.0504

Gnomad AMR exome AF: 0.0778

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.224

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.121 AC: 164719 AN: 1360522 Hom.: 10954 Cov.: 21 AF XY: 0.122 AC XY: 83294 AN XY: 680110

African (AFR) AF: 0.0470 AC: 1413 AN: 30050

American (AMR) AF: 0.0742 AC: 2698 AN: 36380

Ashkenazi Jewish (ASJ) AF: 0.0993 AC: 2421 AN: 24374

East Asian (EAS) AF: 0.243 AC: 9450 AN: 38960

South Asian (SAS) AF: 0.166 AC: 13078 AN: 78566

European-Finnish (FIN) AF: 0.136 AC: 7193 AN: 52888

Middle Eastern (MID) AF: 0.0984 AC: 539 AN: 5476

European-Non Finnish (NFE) AF: 0.117 AC: 121138 AN: 1037068

Other (OTH) AF: 0.120 AC: 6789 AN: 56760

GnomAD4 genome AF: 0.102 AC: 15510 AN: 151886 Hom.: 941 Cov.: 31 AF XY: 0.105 AC XY: 7763 AN XY: 74206

African (AFR) AF: 0.0512 AC: 2120 AN: 41428

American (AMR) AF: 0.0798 AC: 1218 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3468

East Asian (EAS) AF: 0.221 AC: 1140 AN: 5156

South Asian (SAS) AF: 0.163 AC: 782 AN: 4800

European-Finnish (FIN) AF: 0.135 AC: 1423 AN: 10502

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8034 AN: 67952

Other (OTH) AF: 0.0987 AC: 208 AN: 2108

Alfa AF: 0.111 Hom.: 3116

Bravo AF: 0.0947

Asia WGS AF: 0.181 AC: 628 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.48
PhyloP100		-0.50
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: rs3815484; hg19: chr7-36466655; COSMIC: COSV56076610; COSMIC: COSV56076610;