rs3815483

Variant names:

• chr7-36421731-C-G
• rs3815483
• NM_018685.5:c.2164-126C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018685.5(ANLN):​c.2164-126C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 839,016 control chromosomes in the GnomAD database, including 4,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.081 (635 hom., cov: 32)
  • Exomes 𝑓: 0.099 (3660 hom.)
• Consequence: ANLN NM_018685.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.254
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 7-36421731-C-G is Benign according to our data. Variant chr7-36421731-C-G is described in ClinVar as [Benign]. Clinvar id is 1250930.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANLN	NM_018685.5	c.2164-126C>G		intron_variant	Intron 12 of 23	ENST00000265748.7	NP_061155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANLN	ENST00000265748.7	c.2164-126C>G		intron_variant	Intron 12 of 23	1	NM_018685.5	ENSP00000265748.2
ANLN	ENST00000396068.6	c.2053-126C>G		intron_variant	Intron 11 of 22	1		ENSP00000379380.2
ANLN	ENST00000446635.5	c.223-126C>G		intron_variant	Intron 2 of 8	3		ENSP00000400777.1
ANLN	ENST00000428612.5	c.96-2814C>G		intron_variant	Intron 1 of 8	5		ENSP00000413522.1

Frequencies

GnomAD3 genomes AF: 0.0809 AC: 12306 AN: 152114 Hom.: 632 Cov.: 32

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0709

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0941

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0986 AC: 67738 AN: 686784 Hom.: 3660 AF XY: 0.0988 AC XY: 34391 AN XY: 348024

African (AFR) AF: 0.0180 AC: 275 AN: 15278

American (AMR) AF: 0.175 AC: 2757 AN: 15762

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 2317 AN: 13748

East Asian (EAS) AF: 0.155 AC: 4581 AN: 29596

South Asian (SAS) AF: 0.105 AC: 3977 AN: 37970

European-Finnish (FIN) AF: 0.0659 AC: 2676 AN: 40596

Middle Eastern (MID) AF: 0.103 AC: 329 AN: 3198

European-Non Finnish (NFE) AF: 0.0953 AC: 47492 AN: 498316

Other (OTH) AF: 0.103 AC: 3334 AN: 32320

GnomAD4 genome AF: 0.0809 AC: 12314 AN: 152232 Hom.: 635 Cov.: 32 AF XY: 0.0805 AC XY: 5994 AN XY: 74422

African (AFR) AF: 0.0217 AC: 900 AN: 41552

American (AMR) AF: 0.135 AC: 2063 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3472

East Asian (EAS) AF: 0.144 AC: 747 AN: 5178

South Asian (SAS) AF: 0.107 AC: 518 AN: 4828

European-Finnish (FIN) AF: 0.0709 AC: 750 AN: 10584

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0941 AC: 6401 AN: 68010

Other (OTH) AF: 0.108 AC: 229 AN: 2112

Alfa AF: 0.0801 Hom.: 83

Bravo AF: 0.0860

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.2
DANN	Benign	0.69
PhyloP100		-0.25
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: rs3815483; hg19: chr7-36461340; COSMIC: COSV56079706; COSMIC: COSV56079706;