rs1886999

Variant names:

• chr10-29462021-A-G
• rs1886999
• NM_021738.3:c.6402+256T>C

Variant summary

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

The NM_021738.3(SVIL):​c.6402+256T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,144 control chromosomes in the GnomAD database, including 25,073 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 0.56 (25073 hom., cov: 33)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 0 publications found

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:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SVIL	NM_021738.3	c.6402+256T>C		intron_variant	Intron 36 of 37	ENST00000355867.9	NP_068506.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9	c.6402+256T>C		intron_variant	Intron 36 of 37	1	NM_021738.3	ENSP00000348128.4

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84478 AN: 152026 Hom.: 25022 Cov.: 33

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.556 AC: 84597 AN: 152144 Hom.: 25073 Cov.: 33 AF XY: 0.563 AC XY: 41897 AN XY: 74386

African (AFR) AF: 0.755 AC: 31358 AN: 41520

American (AMR) AF: 0.586 AC: 8951 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1108 AN: 3468

East Asian (EAS) AF: 0.579 AC: 3004 AN: 5188

South Asian (SAS) AF: 0.560 AC: 2706 AN: 4830

European-Finnish (FIN) AF: 0.569 AC: 6015 AN: 10576

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29931 AN: 67962

Other (OTH) AF: 0.514 AC: 1084 AN: 2110

Alfa AF: 0.523 Hom.: 2832

Bravo AF: 0.565

Asia WGS AF: 0.557 AC: 1935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.28
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1886999; hg19: chr10-29750950;