chr7-36396387-C-G

Variant names:

• chr7-36396387-C-G
• rs35765596
• NM_018685.5:c.140C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_018685.5(ANLN):​c.140C>G​(p.Ala47Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000445 in 1,596,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: ANLN NM_018685.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2 B:1
• Conservation: PhyloP100: 6.50
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09190199).
• BS2: High AC in GnomAd4 at 32 AD gene.

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.140C>G	p.Ala47Gly	missense	Exon 2 of 24	NP_061155.2
	ANLN	NM_001284301.3		c.140C>G	p.Ala47Gly	missense	Exon 2 of 23	NP_001271230.1	Q9NQW6-2
	ANLN	NM_001284302.3		c.140C>G	p.Ala47Gly	missense	Exon 2 of 23	NP_001271231.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANLN	ENST00000265748.7	TSL:1 MANE Select	c.140C>G	p.Ala47Gly	missense	Exon 2 of 24	ENSP00000265748.2	Q9NQW6-1
	ANLN	ENST00000396068.6	TSL:1	c.140C>G	p.Ala47Gly	missense	Exon 2 of 23	ENSP00000379380.2	Q9NQW6-2
	ANLN	ENST00000918505.1		c.140C>G	p.Ala47Gly	missense	Exon 2 of 26	ENSP00000588564.1

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000441 AC: 11 AN: 249218 AF XY: 0.0000297

Gnomad AFR exome AF: 0.000619

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000270 AC: 39 AN: 1444018 Hom.: 0 Cov.: 30 AF XY: 0.0000209 AC XY: 15 AN XY: 716690

African (AFR) AF: 0.00105 AC: 35 AN: 33234

American (AMR) AF: 0.0000226 AC: 1 AN: 44308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25734

East Asian (EAS) AF: 0.00 AC: 0 AN: 39348

South Asian (SAS) AF: 0.00 AC: 0 AN: 84696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098672

Other (OTH) AF: 0.0000505 AC: 3 AN: 59382

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74344

African (AFR) AF: 0.000772 AC: 32 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000253

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	ANLN-related disorder (1)
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		6.5
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.16
Sift	Uncertain	0.010	D
Sift4G	Benign	0.067	T
Polyphen		0.99	D
Vest4		0.27
MVP		0.55
MPC		0.59
ClinPred		0.21	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.089
Mutation Taster		=72/28	polymorphism

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: rs35765596; hg19: chr7-36435996;