rs1777329

Positions:

• chr10-29622639-G-A
• chr10-29622639-G-T

Variant summary

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

The NM_021738.3(SVIL):​c.-201+11781C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 152,160 control chromosomes in the GnomAD database, including 782 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 0.091 (782 hom., cov: 32)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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]

SVIL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVIL	NM_021738.3	c.-201+11781C>T		intron_variant		ENST00000355867.9	NP_068506.2
SVIL	NM_001323599.2	c.-201+35330C>T		intron_variant			NP_001310528.1
SVIL	NM_001323600.1	c.-201+35330C>T		intron_variant			NP_001310529.1
SVIL	NM_003174.3	c.-201+35330C>T		intron_variant			NP_003165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9	c.-201+11781C>T		intron_variant		1	NM_021738.3	ENSP00000348128.4

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13848 AN: 152042 Hom.: 783 Cov.: 32

Gnomad AFR AF: 0.0613

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0911 AC: 13857 AN: 152160 Hom.: 782 Cov.: 32 AF XY: 0.0889 AC XY: 6614 AN XY: 74384

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0879

Gnomad4 FIN AF: 0.0789

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0889 Hom.: 325

Bravo AF: 0.0940

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.63
DANN	Benign	0.67

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: rs1777329; hg19: chr10-29911568;