rs1021469

Positions:

• chr12-57814381-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
AVIL	NM_006576.4	c.67-155C>T		intron_variant		ENST00000549994.2	NP_006567.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AVIL	ENST00000549994.2	c.67-155C>T		intron_variant		4	NM_006576.4	ENSP00000449239	P1
AVIL	ENST00000257861.7	c.67-155C>T		intron_variant		1		ENSP00000257861	P1
AVIL	ENST00000549851.5	c.182-155C>T		intron_variant, NMD_transcript_variant		2		ENSP00000450188

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

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.320

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.708

Gnomad4 SAS exome AF: 0.448

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.317

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

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.249

Alfa AF: 0.295 Hom.: 7008

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.60
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs1021469; hg19: chr12-58208164;