10-29602392-T-C

Variant names:

• chr10-29602392-T-C
• rs2505901
• NM_021738.3:c.-201+32028A>G

Variant summary

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

The NM_021738.3(SVIL):​c.-201+32028A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 467,648 control chromosomes in the GnomAD database, including 57,518 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 0.48 (18088 hom., cov: 32)
  • Exomes 𝑓: 0.49 (39430 hom.)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 28 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]

MIR938 (HGNC:33681): (microRNA 938) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021738.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVIL	NM_021738.3	MANE Select	c.-201+32028A>G		intron	N/A	NP_068506.2
	SVIL	NM_001323599.2		c.-200-33080A>G		intron	N/A	NP_001310528.1
	SVIL	NM_001323600.1		c.-200-33080A>G		intron	N/A	NP_001310529.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVIL	ENST00000355867.9	TSL:1 MANE Select	c.-201+32028A>G		intron	N/A	ENSP00000348128.4
	SVIL	ENST00000375400.7	TSL:1	c.-200-33080A>G		intron	N/A	ENSP00000364549.3
	SVIL	ENST00000375398.6	TSL:5	c.-201+32028A>G		intron	N/A	ENSP00000364547.3

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73054 AN: 151824 Hom.: 18075 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.466

GnomAD2 exomes AF: 0.484 AC: 98329 AN: 203028 AF XY: 0.485

Gnomad AFR exome AF: 0.401

Gnomad AMR exome AF: 0.513

Gnomad ASJ exome AF: 0.466

Gnomad EAS exome AF: 0.237

Gnomad FIN exome AF: 0.617

Gnomad NFE exome AF: 0.515

Gnomad OTH exome AF: 0.495

GnomAD4 exome AF: 0.493 AC: 155507 AN: 315706 Hom.: 39430 Cov.: 0 AF XY: 0.488 AC XY: 86732 AN XY: 177706

African (AFR) AF: 0.398 AC: 3548 AN: 8914

American (AMR) AF: 0.512 AC: 13425 AN: 26230

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 4738 AN: 10126

East Asian (EAS) AF: 0.232 AC: 2684 AN: 11576

South Asian (SAS) AF: 0.450 AC: 26468 AN: 58860

European-Finnish (FIN) AF: 0.621 AC: 17920 AN: 28874

Middle Eastern (MID) AF: 0.476 AC: 1122 AN: 2358

European-Non Finnish (NFE) AF: 0.509 AC: 78831 AN: 154754

Other (OTH) AF: 0.483 AC: 6771 AN: 14014

GnomAD4 genome AF: 0.481 AC: 73096 AN: 151942 Hom.: 18088 Cov.: 32 AF XY: 0.482 AC XY: 35816 AN XY: 74252

African (AFR) AF: 0.412 AC: 17054 AN: 41430

American (AMR) AF: 0.493 AC: 7526 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1681 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1141 AN: 5154

South Asian (SAS) AF: 0.439 AC: 2117 AN: 4820

European-Finnish (FIN) AF: 0.621 AC: 6544 AN: 10540

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.524 AC: 35619 AN: 67942

Other (OTH) AF: 0.467 AC: 987 AN: 2112

Alfa AF: 0.488 Hom.: 3482

Bravo AF: 0.467

Asia WGS AF: 0.380 AC: 1325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.7
DANN	Benign	0.54
PhyloP100		-0.15
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: rs2505901; hg19: chr10-29891321; COSMIC: COSV63445234; COSMIC: COSV63445234;