rs11172349

Variant names:

• chr12-57818745-G-A
• rs11172349
• NM_006576.4:c.-136C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006576.4(AVIL):​c.-136C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. 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: AVIL NM_006576.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98
• Publications: 24 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)

ACMG classification

Our verdict: Benign. The variant received -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 rank	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 rank	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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 2 AN: 16

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0790 AC: 3281 AN: 41518

American (AMR) AF: 0.256 AC: 3914 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3472

East Asian (EAS) AF: 0.643 AC: 3319 AN: 5164

South Asian (SAS) AF: 0.497 AC: 2398 AN: 4826

European-Finnish (FIN) AF: 0.378 AC: 3992 AN: 10566

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21529 AN: 67982

Other (OTH) AF: 0.237 AC: 499 AN: 2106

Alfa AF: 0.276 Hom.: 8460

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
PhyloP100		3.0
PromoterAI		-0.22	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11172349; hg19: chr12-58212528;