7-36396347-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_018685.5(ANLN):c.100A>G(p.Met34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,609,964 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (6 hom.)
• Consequence: ANLN NM_018685.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.687

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 -16 ACMG points.

• BP6: Variant 7-36396347-A-G is Benign according to our data. Variant chr7-36396347-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1165102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00599 (912/152356) while in subpopulation AFR AF= 0.021 (872/41580). AF 95% confidence interval is 0.0198. There are 9 homozygotes in gnomad4. There are 447 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 907 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANLN	NM_018685.5	c.100A>G	p.Met34Val	missense_variant	2/24	ENST00000265748.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANLN	ENST00000265748.7	c.100A>G	p.Met34Val	missense_variant	2/24	1	NM_018685.5	P2
ANLN	ENST00000396068.6	c.100A>G	p.Met34Val	missense_variant	2/23	1		A2
ANLN	ENST00000424865.1	c.34A>G	p.Met12Val	missense_variant	2/4	3
ANLN	ENST00000418118.1	c.34A>G	p.Met12Val	missense_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.00596 AC: 907 AN: 152238 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00136 AC: 342 AN: 251024 Hom.: 5 AF XY: 0.000921 AC XY: 125 AN XY: 135686

Gnomad AFR exome AF: 0.0187

Gnomad AMR exome AF: 0.000959

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000560 AC: 816 AN: 1457608 Hom.: 6 Cov.: 30 AF XY: 0.000483 AC XY: 350 AN XY: 724966

Gnomad4 AFR exome AF: 0.0204

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000198

Gnomad4 OTH exome AF: 0.00101

GnomAD4 genome AF: 0.00599 AC: 912 AN: 152356 Hom.: 9 Cov.: 32 AF XY: 0.00600 AC XY: 447 AN XY: 74522

Gnomad4 AFR AF: 0.0210

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00110 Hom.: 4

Bravo AF: 0.00651

ESP6500AA AF: 0.0193 AC: 85

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00166 AC: 202

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2021	See Variant Classification Assertion Criteria. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Focal segmental glomerulosclerosis 8 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.77
Cadd	Benign	9.0
Dann	Benign	0.56
DEOGEN2	Benign	0.043	T;.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.57	T;T;T;T
MetaRNN	Benign	0.0024	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.44	N;N;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.65	N;N;N;N
REVEL	Benign	0.010
Sift	Benign	0.25	T;T;T;T
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.0010	B;B;.;.
Vest4		0.062
MVP		0.24
MPC		0.13
ClinPred		0.0044	T
GERP RS		-7.9
Varity_R		0.044
gMVP		0.092

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.49		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.49		Position offset: -5

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

Publications

LitVar

Other links and lift over

dbSNP: rs116131910; hg19: chr7-36435956;