rs1328326

Positions:

• chr10-29570950-G-A
• chr10-29570950-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.-200-1638C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,012 control chromosomes in the GnomAD database, including 22,863 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 0.54 (22863 hom., cov: 33)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVIL	NM_021738.3	c.-200-1638C>T		intron_variant		ENST00000355867.9	NP_068506.2
SVIL	NM_001323599.2	c.-200-1638C>T		intron_variant			NP_001310528.1
SVIL	NM_001323600.1	c.-200-1638C>T		intron_variant			NP_001310529.1
SVIL	NM_003174.3	c.-200-1638C>T		intron_variant			NP_003165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9	c.-200-1638C>T		intron_variant		1	NM_021738.3	ENSP00000348128	A2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82377 AN: 151894 Hom.: 22812 Cov.: 33

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.543 AC: 82486 AN: 152012 Hom.: 22863 Cov.: 33 AF XY: 0.545 AC XY: 40462 AN XY: 74290

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.516

Alfa AF: 0.476 Hom.: 22319

Bravo AF: 0.553

Asia WGS AF: 0.536 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.39

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: rs1328326; hg19: chr10-29859879; COSMIC: COSV63442906; COSMIC: COSV63442906;