rs61549495

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
• Publications: 12 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 -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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANLN	NM_018685.5	MANE Select	c.883_885dupTCT	p.Ser295dup	conservative_inframe_insertion	Exon 5 of 24	NP_061155.2
	ANLN	NM_001284301.3		c.883_885dupTCT	p.Ser295dup	conservative_inframe_insertion	Exon 5 of 23	NP_001271230.1
	ANLN	NM_001284302.3		c.883_885dupTCT	p.Ser295dup	conservative_inframe_insertion	Exon 5 of 23	NP_001271231.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANLN	ENST00000265748.7	TSL:1 MANE Select	c.883_885dupTCT	p.Ser295dup	conservative_inframe_insertion	Exon 5 of 24	ENSP00000265748.2
	ANLN	ENST00000396068.6	TSL:1	c.883_885dupTCT	p.Ser295dup	conservative_inframe_insertion	Exon 5 of 23	ENSP00000379380.2
	ANLN	ENST00000429082.1	TSL:4	n.191_193dupTCT		non_coding_transcript_exon	Exon 2 of 3	ENSP00000398712.1

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

African (AFR) AF: 0.334 AC: 11114 AN: 33290

American (AMR) AF: 0.538 AC: 24044 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 12214 AN: 26076

East Asian (EAS) AF: 0.587 AC: 23235 AN: 39604

South Asian (SAS) AF: 0.445 AC: 38312 AN: 86018

European-Finnish (FIN) AF: 0.378 AC: 20148 AN: 53328

Middle Eastern (MID) AF: 0.388 AC: 2228 AN: 5746

European-Non Finnish (NFE) AF: 0.388 AC: 429330 AN: 1105692

Other (OTH) 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

African (AFR) AF: 0.335 AC: 13865 AN: 41388

American (AMR) AF: 0.445 AC: 6784 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1622 AN: 3462

East Asian (EAS) AF: 0.584 AC: 2995 AN: 5126

South Asian (SAS) AF: 0.456 AC: 2192 AN: 4812

European-Finnish (FIN) AF: 0.371 AC: 3894 AN: 10510

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26465 AN: 67836

Other (OTH) AF: 0.406 AC: 855 AN: 2108

Alfa AF: 0.405 Hom.: 8043

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Focal segmental glomerulosclerosis 8 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.59
Mutation Taster		=79/21	polymorphism (auto)

Splicing

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

Other links and lift over

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