7-36450989-G-T

Variant names:

• chr7-36450989-G-T
• rs3801303
• NM_018685.5:c.3251+1152G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018685.5(ANLN):​c.3251+1152G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,080 control chromosomes in the GnomAD database, including 18,876 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (18876 hom., cov: 32)
• Consequence: ANLN NM_018685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANLN	NM_018685.5	c.3251+1152G>T		intron_variant	Intron 23 of 23	ENST00000265748.7	NP_061155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANLN	ENST00000265748.7	c.3251+1152G>T		intron_variant	Intron 23 of 23	1	NM_018685.5	ENSP00000265748.2
ANLN	ENST00000396068.6	c.3140+1152G>T		intron_variant	Intron 22 of 22	1		ENSP00000379380.2
ANLN	ENST00000491782.1	n.899+1152G>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75300 AN: 151962 Hom.: 18847 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.487

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.496 AC: 75390 AN: 152080 Hom.: 18876 Cov.: 32 AF XY: 0.499 AC XY: 37118 AN XY: 74328

African (AFR) AF: 0.436 AC: 18080 AN: 41462

American (AMR) AF: 0.508 AC: 7770 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1896 AN: 3472

East Asian (EAS) AF: 0.635 AC: 3288 AN: 5174

South Asian (SAS) AF: 0.591 AC: 2849 AN: 4822

European-Finnish (FIN) AF: 0.526 AC: 5559 AN: 10560

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34211 AN: 67980

Other (OTH) AF: 0.486 AC: 1028 AN: 2116

Alfa AF: 0.501 Hom.: 3403

Bravo AF: 0.493

Asia WGS AF: 0.604 AC: 2098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		0.58
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: rs3801303; hg19: chr7-36490598;