rs3815483

Positions:

• chr7-36421731-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
ANLN	NM_018685.5	c.2164-126C>G		intron_variant		ENST00000265748.7	NP_061155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANLN	ENST00000265748.7	c.2164-126C>G		intron_variant		1	NM_018685.5	ENSP00000265748	P2
ANLN	ENST00000396068.6	c.2053-126C>G		intron_variant		1		ENSP00000379380	A2
ANLN	ENST00000428612.5	c.97-2814C>G		intron_variant		5		ENSP00000413522
ANLN	ENST00000446635.5	c.225-126C>G		intron_variant		3		ENSP00000400777

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

Gnomad4 AFR exome AF: 0.0180

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0659

Gnomad4 NFE exome AF: 0.0953

Gnomad4 OTH exome AF: 0.103

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

Gnomad4 AFR AF: 0.0217

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0709

Gnomad4 NFE AF: 0.0941

Gnomad4 OTH AF: 0.108

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.2
DANN	Benign	0.69

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: rs3815483; hg19: chr7-36461340; COSMIC: COSV56079706; COSMIC: COSV56079706;