rs11172349

Positions:

• chr12-57818745-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.265 in 152,134 control chromosomes in the GnomAD database, including 6,748 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (6748 hom., cov: 31)
  • Exomes 𝑓: 0.091 (0 hom.)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98

Genes affected

(HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AVIL	NM_006576.4	c.-136C>T		upstream_gene_variant		ENST00000549994.2	NP_006567.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AVIL	ENST00000549994.2	c.-136C>T		upstream_gene_variant		4	NM_006576.4	ENSP00000449239.2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40284 AN: 151994 Hom.: 6746 Cov.: 31

Gnomad AFR AF: 0.0792

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.0909 AC: 2 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.111 AC XY: 2 AN XY: 18

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.265 AC: 40291 AN: 152112 Hom.: 6748 Cov.: 31 AF XY: 0.273 AC XY: 20331 AN XY: 74348

Gnomad4 AFR AF: 0.0790

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.237

Alfa AF: 0.300 Hom.: 6277

Bravo AF: 0.246

Asia WGS AF: 0.517 AC: 1795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11172349; hg19: chr12-58212528;