10-29545069-A-G

Position:

• chr10-29545069-A-G

Variant summary

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

The NM_021738.3(SVIL):​c.827+5528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 533,780 control chromosomes in the GnomAD database, including 22,724 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 0.30 (7075 hom., cov: 31)
  • Exomes 𝑓: 0.28 (15649 hom.)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

Genes affected

SVIL (HGNC:11480): (supervillin) This gene encodes a bipartite protein with distinct amino- and carboxy-terminal domains. The amino-terminus contains nuclear localization signals and the carboxy-terminus contains numerous consecutive sequences with extensive similarity to proteins in the gelsolin family of actin-binding proteins, which cap, nucleate, and/or sever actin filaments. The gene product is tightly associated with both actin filaments and plasma membranes, suggesting a role as a high-affinity link between the actin cytoskeleton and the membrane. The encoded protein appears to aid in both myosin II assembly during cell spreading and disassembly of focal adhesions. Several transcript variants encoding different isoforms of supervillin have been described. [provided by RefSeq, Apr 2016]

MIR604 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVIL	NM_021738.3	c.827+5528T>C		intron_variant		ENST00000355867.9	NP_068506.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9	c.827+5528T>C		intron_variant		1	NM_021738.3	ENSP00000348128.4

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45824 AN: 151708 Hom.: 7069 Cov.: 31

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.277

GnomAD3 exomes AF: 0.287 AC: 71775 AN: 250498 Hom.: 10572 AF XY: 0.282 AC XY: 38280 AN XY: 135612

Gnomad AFR exome AF: 0.385

Gnomad AMR exome AF: 0.302

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.340

Gnomad SAS exome AF: 0.318

Gnomad FIN exome AF: 0.312

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.270

GnomAD4 exome AF: 0.281 AC: 107388 AN: 381954 Hom.: 15649 Cov.: 0 AF XY: 0.281 AC XY: 61032 AN XY: 217450

Gnomad4 AFR exome AF: 0.385

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.310

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.302 AC: 45848 AN: 151826 Hom.: 7075 Cov.: 31 AF XY: 0.304 AC XY: 22553 AN XY: 74220

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.276

Alfa AF: 0.275 Hom.: 2793

Bravo AF: 0.305

Asia WGS AF: 0.344 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.0
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2368393; hg19: chr10-29833998; COSMIC: COSV63441407;