7-36407740-A-ACTT

Variant names:

• chr7-36407740-A-ACTT
• rs61549495
• NM_018685.5:c.883_885dupTCT

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BA1

The NM_018685.5(ANLN):​c.883_885dupTCT​(p.Ser295dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,606,298 control chromosomes in the GnomAD database, including 131,825 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11794 hom., cov: 0)
  • Exomes 𝑓: 0.40 (120031 hom.)
• Consequence: ANLN NM_018685.5 conservative_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.593

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

Our verdict: Benign. The variant received -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_018685.5. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 7-36407740-A-ACTT is Benign according to our data. Variant chr7-36407740-A-ACTT is described in ClinVar as [Benign]. Clinvar id is 261052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANLN	NM_018685.5	c.883_885dupTCT	p.Ser295dup	conservative_inframe_insertion	Exon 5 of 24	ENST00000265748.7	NP_061155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANLN	ENST00000265748.7	c.883_885dupTCT	p.Ser295dup	conservative_inframe_insertion	Exon 5 of 24	1	NM_018685.5	ENSP00000265748.2

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59157 AN: 151578 Hom.: 11780 Cov.: 0

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.405

GnomAD2 exomes AF: 0.434 AC: 108843 AN: 250590 AF XY: 0.430

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.553

Gnomad ASJ exome AF: 0.469

Gnomad EAS exome AF: 0.600

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.388

Gnomad OTH exome AF: 0.434

GnomAD4 exome AF: 0.402 AC: 585388 AN: 1454602 Hom.: 120031 Cov.: 32 AF XY: 0.404 AC XY: 292228 AN XY: 724078

Gnomad4 AFR exome AF: 0.334 AC: 11114 AN: 33290

Gnomad4 AMR exome AF: 0.538 AC: 24044 AN: 44686

Gnomad4 ASJ exome AF: 0.468 AC: 12214 AN: 26076

Gnomad4 EAS exome AF: 0.587 AC: 23235 AN: 39604

Gnomad4 SAS exome AF: 0.445 AC: 38312 AN: 86018

Gnomad4 FIN exome AF: 0.378 AC: 20148 AN: 53328

Gnomad4 NFE exome AF: 0.388 AC: 429330 AN: 1105692

Gnomad4 Remaining exome AF: 0.412 AC: 24763 AN: 60162

GnomAD4 genome AF: 0.390 AC: 59224 AN: 151696 Hom.: 11794 Cov.: 0 AF XY: 0.393 AC XY: 29103 AN XY: 74140

Gnomad4 AFR AF: 0.335 AC: 0.335 AN: 0.335

Gnomad4 AMR AF: 0.445 AC: 0.444736 AN: 0.444736

Gnomad4 ASJ AF: 0.469 AC: 0.468515 AN: 0.468515

Gnomad4 EAS AF: 0.584 AC: 0.584276 AN: 0.584276

Gnomad4 SAS AF: 0.456 AC: 0.455528 AN: 0.455528

Gnomad4 FIN AF: 0.371 AC: 0.370504 AN: 0.370504

Gnomad4 NFE AF: 0.390 AC: 0.390132 AN: 0.390132

Gnomad4 OTH AF: 0.406 AC: 0.405598 AN: 0.405598

Alfa AF: 0.405 Hom.: 8043

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Focal segmental glomerulosclerosis 8 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=79/21	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61549495; hg19: chr7-36447349; COSMIC: COSV56073563; COSMIC: COSV56073563;