chr7-36396136-C-G

Variant names:

• chr7-36396136-C-G
• rs10215150
• NM_018685.5:c.19-130C>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.19-130C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 639,314 control chromosomes in the GnomAD database, including 11,681 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2819 hom., cov: 32)
  • Exomes 𝑓: 0.18 (8862 hom.)
• Consequence: ANLN NM_018685.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.252
• Publications: 0 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=-0.86).
• BP6: Variant 7-36396136-C-G is Benign according to our data. Variant chr7-36396136-C-G is described in ClinVar as Benign. ClinVar VariationId is 1221148.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANLN	NM_018685.5	MANE Select	c.19-130C>G		intron	N/A	NP_061155.2
	ANLN	NM_001284301.3		c.19-130C>G		intron	N/A	NP_001271230.1	Q9NQW6-2
	ANLN	NM_001284302.3		c.19-130C>G		intron	N/A	NP_001271231.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANLN	ENST00000265748.7	TSL:1 MANE Select	c.19-130C>G		intron	N/A	ENSP00000265748.2	Q9NQW6-1
	ANLN	ENST00000396068.6	TSL:1	c.19-130C>G		intron	N/A	ENSP00000379380.2	Q9NQW6-2
	ANLN	ENST00000918505.1		c.19-130C>G		intron	N/A	ENSP00000588564.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28082 AN: 151980 Hom.: 2816 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.182 AC: 88475 AN: 487218 Hom.: 8862 AF XY: 0.181 AC XY: 44186 AN XY: 243802

African (AFR) AF: 0.187 AC: 2248 AN: 12034

American (AMR) AF: 0.222 AC: 2347 AN: 10576

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 2252 AN: 11182

East Asian (EAS) AF: 0.392 AC: 10110 AN: 25784

South Asian (SAS) AF: 0.265 AC: 3896 AN: 14712

European-Finnish (FIN) AF: 0.186 AC: 6620 AN: 35502

Middle Eastern (MID) AF: 0.164 AC: 319 AN: 1944

European-Non Finnish (NFE) AF: 0.160 AC: 56135 AN: 351360

Other (OTH) AF: 0.189 AC: 4548 AN: 24124

GnomAD4 genome AF: 0.185 AC: 28103 AN: 152096 Hom.: 2819 Cov.: 32 AF XY: 0.191 AC XY: 14186 AN XY: 74342

African (AFR) AF: 0.183 AC: 7598 AN: 41478

American (AMR) AF: 0.215 AC: 3291 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 706 AN: 3472

East Asian (EAS) AF: 0.412 AC: 2129 AN: 5170

South Asian (SAS) AF: 0.271 AC: 1302 AN: 4812

European-Finnish (FIN) AF: 0.184 AC: 1944 AN: 10576

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.156 AC: 10600 AN: 67998

Other (OTH) AF: 0.167 AC: 352 AN: 2112

Alfa AF: 0.0728 Hom.: 87

Bravo AF: 0.186

Asia WGS AF: 0.333 AC: 1156 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.40
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: rs10215150; hg19: chr7-36435745;