rs1021469

Variant names:

• chr12-57814381-G-A
• rs1021469
• NM_006576.4:c.67-155C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-57814381-G-A
• chr12-57814381-G-C
• chr12-57814381-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006576.4(AVIL):​c.67-155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 702,464 control chromosomes in the GnomAD database, including 43,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7025 hom., cov: 32)
  • Exomes 𝑓: 0.34 (36036 hom.)
• Consequence: AVIL NM_006576.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.727
• Publications: 36 publications found

Genes affected

AVIL (HGNC:14188): (advillin) The protein encoded by this gene is a member of the gelsolin/villin family of actin regulatory proteins. This protein has structural similarity to villin. It binds actin and may play a role in the development of neuronal cells that form ganglia. [provided by RefSeq, Jul 2008]

AVIL Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 21

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000269903 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-57814381-G-A is Benign according to our data. Variant chr12-57814381-G-A is described in ClinVar as Benign. ClinVar VariationId is 1286130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AVIL	NM_006576.4	c.67-155C>T		intron_variant	Intron 2 of 19	ENST00000549994.2	NP_006567.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVIL	ENST00000549994.2	c.67-155C>T		intron_variant	Intron 2 of 19	4	NM_006576.4	ENSP00000449239.2

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43600 AN: 151876 Hom.: 7019 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.345 AC: 189651 AN: 550470 Hom.: 36036 Cov.: 7 AF XY: 0.350 AC XY: 100509 AN XY: 286768

African (AFR) AF: 0.169 AC: 2449 AN: 14504

American (AMR) AF: 0.320 AC: 7465 AN: 23326

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 3995 AN: 14696

East Asian (EAS) AF: 0.708 AC: 21757 AN: 30732

South Asian (SAS) AF: 0.448 AC: 23256 AN: 51868

European-Finnish (FIN) AF: 0.347 AC: 10196 AN: 29354

Middle Eastern (MID) AF: 0.187 AC: 648 AN: 3472

European-Non Finnish (NFE) AF: 0.313 AC: 110689 AN: 353508

Other (OTH) AF: 0.317 AC: 9196 AN: 29010

GnomAD4 genome AF: 0.287 AC: 43634 AN: 151994 Hom.: 7025 Cov.: 32 AF XY: 0.295 AC XY: 21911 AN XY: 74292

African (AFR) AF: 0.171 AC: 7084 AN: 41444

American (AMR) AF: 0.263 AC: 4006 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 923 AN: 3470

East Asian (EAS) AF: 0.645 AC: 3330 AN: 5164

South Asian (SAS) AF: 0.456 AC: 2192 AN: 4804

European-Finnish (FIN) AF: 0.375 AC: 3967 AN: 10576

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21191 AN: 67964

Other (OTH) AF: 0.249 AC: 525 AN: 2108

Alfa AF: 0.282 Hom.: 10044

Bravo AF: 0.273

Asia WGS AF: 0.507 AC: 1760 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.60
DANN	Benign	0.62
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1021469; hg19: chr12-58208164;