10-29458551-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_021738.3(SVIL):c.6441C>T(p.Asp2147=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000791 in 1,612,482 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (13 hom.)
• Consequence: SVIL NM_021738.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94

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-AS1 (HGNC:51219): (SVIL antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 10-29458551-G-A is Benign according to our data. Variant chr10-29458551-G-A is described in ClinVar as [Benign]. Clinvar id is 717933.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.94 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0011 (167/152328) while in subpopulation EAS AF= 0.0151 (78/5166). AF 95% confidence interval is 0.0124. There are 0 homozygotes in gnomad4. There are 109 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SVIL	NM_021738.3	c.6441C>T	p.Asp2147=	synonymous_variant	37/38	ENST00000355867.9
SVIL-AS1	NR_110927.1	n.182-28604G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SVIL	ENST00000355867.9	c.6441C>T	p.Asp2147=	synonymous_variant	37/38	1	NM_021738.3	A2
SVIL-AS1	ENST00000684815.1	n.236+43139G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 167 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0151

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00724

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00194 AC: 484 AN: 249232 Hom.: 4 AF XY: 0.00169 AC XY: 228 AN XY: 134676

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000603

Gnomad EAS exome AF: 0.0162

Gnomad SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.00659

Gnomad NFE exome AF: 0.000284

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000759 AC: 1108 AN: 1460154 Hom.: 13 Cov.: 32 AF XY: 0.000741 AC XY: 538 AN XY: 726272

Gnomad4 AFR exome AF: 0.0000898

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000461

Gnomad4 EAS exome AF: 0.0155

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00583

Gnomad4 NFE exome AF: 0.0000900

Gnomad4 OTH exome AF: 0.000928

GnomAD4 genome AF: 0.00110 AC: 167 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.00146 AC XY: 109 AN XY: 74478

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0151

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00724

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000244 Hom.: 0

Bravo AF: 0.000839

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	2.5
Dann	Benign	0.91

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: rs138190166; hg19: chr10-29747480; COSMIC: COSV100881476; COSMIC: COSV100881476;